4-143436584-A-G

Variant names:

• chr4-143436584-A-G
• rs3805236
• NM_002039.4:c.594-1415A>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.594-1415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 151,980 control chromosomes in the GnomAD database, including 41,881 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 0.73 (41881 hom., cov: 30)
• Consequence: GAB1 NM_002039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 26 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB1	NM_002039.4	MANE Select	c.594-1415A>G		intron	N/A	NP_002030.2
	GAB1	NM_207123.3		c.594-1415A>G		intron	N/A	NP_997006.1	Q13480-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB1	ENST00000262994.9	TSL:1 MANE Select	c.594-1415A>G		intron	N/A	ENSP00000262994.4	Q13480-1
	GAB1	ENST00000262995.9	TSL:1	c.594-1415A>G		intron	N/A	ENSP00000262995.4	Q13480-2
	GAB1	ENST00000882513.1		c.675-1415A>G		intron	N/A	ENSP00000552572.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110290 AN: 151862 Hom.: 41833 Cov.: 30

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.726 AC: 110393 AN: 151980 Hom.: 41881 Cov.: 30 AF XY: 0.718 AC XY: 53350 AN XY: 74268

African (AFR) AF: 0.940 AC: 38992 AN: 41488

American (AMR) AF: 0.614 AC: 9353 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2241 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1525 AN: 5148

South Asian (SAS) AF: 0.702 AC: 3369 AN: 4796

European-Finnish (FIN) AF: 0.610 AC: 6433 AN: 10554

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.680 AC: 46236 AN: 67992

Other (OTH) AF: 0.718 AC: 1509 AN: 2102

Alfa AF: 0.692 Hom.: 142478

Bravo AF: 0.733

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.77
DANN	Benign	0.37
PhyloP100		0.096
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: rs3805236; hg19: chr4-144357737;