4-143415931-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002039.4(GAB1):c.367+164dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 152,186 control chromosomes in the GnomAD database, including 770 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.085 (770 hom., cov: 31)
• Consequence: GAB1 NM_002039.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.151

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 -10 ACMG points.

• BP6: Variant 4-143415931-T-TG is Benign according to our data. Variant chr4-143415931-T-TG is described in ClinVar as [Benign]. Clinvar id is 1226118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAB1	NM_002039.4	c.367+164dup		intron_variant		ENST00000262994.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAB1	ENST00000262994.9	c.367+164dup		intron_variant		1	NM_002039.4	A1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12858 AN: 152068 Hom.: 770 Cov.: 31

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0846 AC: 12868 AN: 152186 Hom.: 770 Cov.: 31 AF XY: 0.0841 AC XY: 6255 AN XY: 74392

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0571

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0465

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.0493

Gnomad4 OTH AF: 0.0821

Alfa AF: 0.0707 Hom.: 56

Bravo AF: 0.0866

Asia WGS AF: 0.0240 AC: 84 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs138154602; hg19: chr4-144337084;