rs3805246

Positions:

• chr4-143382955-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB1	NM_002039.4	c.73-32522G>A		intron_variant		ENST00000262994.9	NP_002030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB1	ENST00000262994.9	c.73-32522G>A		intron_variant		1	NM_002039.4	ENSP00000262994	A1

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

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.336

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.67

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: rs3805246; hg19: chr4-144304108;