chr3-160375890-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020800.3(IFT80):c.371-10C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00548 in 1,558,710 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 32 hom. )

Consequence

IFT80
NM_020800.3 intron

Scores

Splicing: ADA: 0.01914

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.110

Publications

1 publications found

Variant links:

Genes affected

IFT80 (HGNC:29262): (intraflagellar transport 80) The protein encoded by this gene is part of the intraflagellar transport complex B and is necessary for the function of motile and sensory cilia. Defects in this gene are a cause of asphyxiating thoracic dystrophy 2 (ATD2). Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Jun 2010]

IFT80 links:

TRIM59-IFT80 (HGNC:56756): (TRIM59-IFT80 readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring TRIM59 (tripartite motif containing 59) and IFT80 (intraflagellar transport 80) genes on chromosome 3. The readthrough transcript is unlikely to produce a protein product. [provided by RefSeq, Jun 2017]

TRIM59-IFT80 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 3-160375890-G-T is Benign according to our data. Variant chr3-160375890-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 284855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00422 (634/150126) while in subpopulation NFE AF = 0.00634 (427/67354). AF 95% confidence interval is 0.00584. There are 3 homozygotes in GnomAd4. There are 327 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT80	NM_020800.3 link	c.371-10C>A		intron_variant	Intron 4 of 19	ENST00000326448.12	NP_065851.1	Q9P2H3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448.12 link	c.371-10C>A		intron_variant	Intron 4 of 19	1	NM_020800.3	ENSP00000312778.7		Q9P2H3-1
TRIM59-IFT80	ENST00000483754.1 link	n.953-9738C>A		intron_variant	Intron 3 of 18	2		ENSP00000456272.1		H3BRJ5

Frequencies

GnomAD3 genomes

AF:

0.00423

AC:

634

AN:

150022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00292

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00549

Gnomad FIN

AF:

0.00715

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00634

Gnomad OTH

AF:

0.00390

GnomAD2 exomes

AF:

0.00436

AC:

972

AN:

222694

AF XY:

0.00473

show subpopulations

Gnomad AFR exome

AF:

0.000716

Gnomad AMR exome

AF:

0.00267

Gnomad ASJ exome

AF:

0.00118

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00627

Gnomad NFE exome

AF:

0.00602

Gnomad OTH exome

AF:

0.00444

GnomAD4 exome

AF:

0.00561

AC:

7900

AN:

1408584

Hom.:

Cov.:

AF XY:

0.00567

AC XY:

3988

AN XY:

702846

show subpopulations

African (AFR)

AF:

0.000968

AC:

AN:

32024

American (AMR)

AF:

0.00244

AC:

106

AN:

43402

Ashkenazi Jewish (ASJ)

AF:

0.00106

AC:

AN:

25474

East Asian (EAS)

AF:

0.00

AC:

AN:

38786

South Asian (SAS)

AF:

0.00439

AC:

366

AN:

83430

European-Finnish (FIN)

AF:

0.00544

AC:

288

AN:

52928

Middle Eastern (MID)

AF:

0.00126

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

0.00638

AC:

6815

AN:

1068762

Other (OTH)

AF:

0.00447

AC:

260

AN:

58224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

311

622

933

1244

1555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00422

AC:

634

AN:

150126

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

327

AN XY:

73280

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

41040

American (AMR)

AF:

0.00292

AC:

AN:

15084

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00550

AC:

AN:

4724

European-Finnish (FIN)

AF:

0.00715

AC:

AN:

10064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00634

AC:

427

AN:

67354

Other (OTH)

AF:

0.00386

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00438

Hom.:

Bravo

AF:

0.00350

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Asphyxiating thoracic dystrophy 2

Benign:2

Oct 20, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IFT80: BS2 -

not specified

Benign:1

Dec 07, 2015

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jeune thoracic dystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Connective tissue disorder

Benign:1

Jan 21, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.019

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr3-160375890-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over