rs7663712

Variant names:

• chr4-143339964-A-G
• rs7663712
• NM_002039.4:c.72+2704A>G

Variant summary

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

The NM_002039.4(GAB1):​c.72+2704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 152,312 control chromosomes in the GnomAD database, including 179 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 0.046 (179 hom., cov: 33)
• Consequence: GAB1 NM_002039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB1	NM_002039.4	c.72+2704A>G		intron_variant	Intron 1 of 9	ENST00000262994.9	NP_002030.2
GAB1	NM_207123.3	c.72+2704A>G		intron_variant	Intron 1 of 10		NP_997006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB1	ENST00000262994.9	c.72+2704A>G		intron_variant	Intron 1 of 9	1	NM_002039.4	ENSP00000262994.4
GAB1	ENST00000262995.9	c.72+2704A>G		intron_variant	Intron 1 of 10	1		ENSP00000262995.4
GAB1	ENST00000514639.6	c.72+2704A>G		intron_variant	Intron 1 of 10	3		ENSP00000427435.2

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6970 AN: 152194 Hom.: 179 Cov.: 33

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0458 AC: 6980 AN: 152312 Hom.: 179 Cov.: 33 AF XY: 0.0444 AC XY: 3305 AN XY: 74490

African (AFR) AF: 0.0464 AC: 1929 AN: 41580

American (AMR) AF: 0.0428 AC: 655 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3472

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5186

South Asian (SAS) AF: 0.0545 AC: 263 AN: 4824

European-Finnish (FIN) AF: 0.0185 AC: 196 AN: 10620

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0529 AC: 3600 AN: 68010

Other (OTH) AF: 0.0483 AC: 102 AN: 2112

Alfa AF: 0.0512 Hom.: 46

Bravo AF: 0.0463

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.1
DANN	Benign	0.63
PhyloP100		0.073
Mutation Taster		=100/0	polymorphism

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: rs7663712; hg19: chr4-144261117;