NM_002039.4:c.73-32522G>A

Variant names:

• chr4-143382955-G-A
• rs3805246
• NM_002039.4:c.73-32522G>A

Variant summary

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

The NM_002039.4(GAB1):​c.73-32522G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,952 control chromosomes in the GnomAD database, including 7,888 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 0.32 (7888 hom., cov: 32)
• Consequence: GAB1 NM_002039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002039.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB1	NM_002039.4	MANE Select	c.73-32522G>A		intron	N/A	NP_002030.2
	GAB1	NM_207123.3		c.73-32522G>A		intron	N/A	NP_997006.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB1	ENST00000262994.9	TSL:1 MANE Select	c.73-32522G>A		intron	N/A	ENSP00000262994.4
	GAB1	ENST00000262995.9	TSL:1	c.73-32522G>A		intron	N/A	ENSP00000262995.4
	GAB1	ENST00000515388.1	TSL:1	n.83+925G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48107 AN: 151834 Hom.: 7892 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.317 AC: 48134 AN: 151952 Hom.: 7888 Cov.: 32 AF XY: 0.319 AC XY: 23674 AN XY: 74254

African (AFR) AF: 0.241 AC: 9971 AN: 41428

American (AMR) AF: 0.321 AC: 4894 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1302 AN: 3464

East Asian (EAS) AF: 0.268 AC: 1387 AN: 5174

South Asian (SAS) AF: 0.484 AC: 2333 AN: 4820

European-Finnish (FIN) AF: 0.318 AC: 3361 AN: 10554

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23735 AN: 67940

Other (OTH) AF: 0.336 AC: 708 AN: 2108

Alfa AF: 0.340 Hom.: 1429

Bravo AF: 0.310

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.67
PhyloP100		-0.025
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: rs3805246; hg19: chr4-144304108;