chr4-143436584-A-G

Position:

• chr4-143436584-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB1	NM_002039.4	c.594-1415A>G		intron_variant		ENST00000262994.9	NP_002030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB1	ENST00000262994.9	c.594-1415A>G		intron_variant		1	NM_002039.4	ENSP00000262994.4

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

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.718

Alfa AF: 0.687 Hom.: 58929

Bravo AF: 0.733

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.77
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs3805236; hg19: chr4-144357737;