chr3-160375890-G-T

Position:

chr3-160375890-G-T

Variant summary

Our verdict is Benign. Variant got -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

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:

ENSG00000248710 (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]

ENSG00000248710 links:

IFT80 (HGNC:):

IFT80 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr3-160375890-G-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT80	NM_020800.3 linkuse as main transcript	c.371-10C>A		intron_variant		ENST00000326448.12	NP_065851.1	Q9P2H3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448.12 linkuse as main transcript	c.371-10C>A		intron_variant		1	NM_020800.3	ENSP00000312778.7		Q9P2H3-1
ENSG00000248710	ENST00000483754.1 linkuse as main transcript	n.953-9738C>A		intron_variant		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

GnomAD3 exomes

AF:

0.00436

AC:

972

AN:

222694

Hom.:

AF XY:

0.00473

AC XY:

571

AN XY:

120682

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 SAS exome

AF:

0.00424

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

Gnomad4 AFR exome

AF:

0.000968

Gnomad4 AMR exome

AF:

0.00244

Gnomad4 ASJ exome

AF:

0.00106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00439

Gnomad4 FIN exome

AF:

0.00544

Gnomad4 NFE exome

AF:

0.00638

Gnomad4 OTH exome

AF:

0.00447

GnomAD4 genome

AF:

0.00422

AC:

634

AN:

150126

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

327

AN XY:

73280

show subpopulations

Gnomad4 AFR

AF:

0.00129

Gnomad4 AMR

AF:

0.00292

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00550

Gnomad4 FIN

AF:

0.00715

Gnomad4 NFE

AF:

0.00634

Gnomad4 OTH

AF:

0.00386

Alfa

AF:

0.00470

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

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 20, 2023	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	IFT80: BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 07, 2015

- -

Jeune thoracic dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 21, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over