rs1397527

Variant names:

• chr4-143405232-G-T
• rs1397527
• NM_002039.4:c.73-10245G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002039.4(GAB1):​c.73-10245G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,330 control chromosomes in the GnomAD database, including 23,873 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23873 hom., cov: 32)
• Consequence: GAB1 NM_002039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 4 publications found

Genes affected

GAB1 (HGNC:4066): (GRB2 associated binding protein 1) The protein encoded by this gene is a member of the IRS1-like multisubstrate docking protein family. It is an important mediator of branching tubulogenesis and plays a central role in cellular growth response, transformation and apoptosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

GAB1 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 26

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB1	NM_002039.4	c.73-10245G>T		intron_variant	Intron 1 of 9	ENST00000262994.9	NP_002030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB1	ENST00000262994.9	c.73-10245G>T		intron_variant	Intron 1 of 9	1	NM_002039.4	ENSP00000262994.4

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82347 AN: 151216 Hom.: 23833 Cov.: 32

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.546

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.545 AC: 82446 AN: 151330 Hom.: 23873 Cov.: 32 AF XY: 0.542 AC XY: 40042 AN XY: 73888

African (AFR) AF: 0.752 AC: 31059 AN: 41312

American (AMR) AF: 0.487 AC: 7413 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1812 AN: 3466

East Asian (EAS) AF: 0.304 AC: 1562 AN: 5132

South Asian (SAS) AF: 0.620 AC: 2973 AN: 4792

European-Finnish (FIN) AF: 0.396 AC: 4104 AN: 10360

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31732 AN: 67744

Other (OTH) AF: 0.546 AC: 1151 AN: 2108

Alfa AF: 0.514 Hom.: 2574

Bravo AF: 0.555

Asia WGS AF: 0.527 AC: 1833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.61
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1397527; hg19: chr4-144326385; COSMIC: COSV53754692;