Variant 3-160257321-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020800.3(IFT80):c.*1204G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 152,044 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

IFT80
NM_020800.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.933

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:):

TRIM59-IFT80 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-160257321-C-T is Benign according to our data. Variant chr3-160257321-C-T is described in ClinVar as [Benign]. Clinvar id is 901996.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00403 (613/152044) while in subpopulation EAS AF= 0.0241 (125/5176). AF 95% confidence interval is 0.0207. There are 2 homozygotes in gnomad4. There are 323 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT80	NM_020800.3 linkuse as main transcript	c.*1204G>A		3_prime_UTR_variant	20/20	ENST00000326448.12
TRIM59-IFT80	NR_148401.1 linkuse as main transcript	n.3100+1146G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT80	ENST00000326448.12 linkuse as main transcript	c.*1204G>A		3_prime_UTR_variant	20/20	1	NM_020800.3	P1	Q9P2H3-1
IFT80	ENST00000483465.5 linkuse as main transcript	c.*1204G>A		3_prime_UTR_variant	19/19	1			Q9P2H3-2

Frequencies

GnomAD3 genomes

AF:

0.00402

AC:

610

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00660

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.0241

Gnomad SAS

AF:

0.00438

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00174

Gnomad OTH

AF:

0.00479

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.00403

AC:

613

AN:

152044

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

323

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00665

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.0241

Gnomad4 SAS

AF:

0.00438

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00174

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00355

Hom.:

Bravo

AF:

0.00433

Asia WGS

AF:

0.0210

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Asphyxiating thoracic dystrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.34

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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