4-143439755-G-A

Position:

• chr4-143439755-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002039.4(GAB1):​c.1196-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,336,290 control chromosomes in the GnomAD database, including 608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (91 hom., cov: 32)
  • Exomes 𝑓: 0.010 (517 hom.)
• Consequence: GAB1 NM_002039.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.577

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-143439755-G-A is Benign according to our data. Variant chr4-143439755-G-A is described in ClinVar as [Benign]. Clinvar id is 1278037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAB1	NM_002039.4	c.1196-47G>A		intron_variant		ENST00000262994.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAB1	ENST00000262994.9	c.1196-47G>A		intron_variant		1	NM_002039.4	A1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1954 AN: 152176 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0890

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00606

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.0243 AC: 5858 AN: 240880 Hom.: 424 AF XY: 0.0193 AC XY: 2505 AN XY: 130124

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.00143

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.00271

Gnomad FIN exome AF: 0.00294

Gnomad NFE exome AF: 0.00603

Gnomad OTH exome AF: 0.0198

GnomAD4 exome AF: 0.0101 AC: 11949 AN: 1183996 Hom.: 517 Cov.: 16 AF XY: 0.00914 AC XY: 5505 AN XY: 602544

Gnomad4 AFR exome AF: 0.00178

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.00144

Gnomad4 EAS exome AF: 0.000366

Gnomad4 SAS exome AF: 0.00353

Gnomad4 FIN exome AF: 0.00303

Gnomad4 NFE exome AF: 0.00591

Gnomad4 OTH exome AF: 0.00796

GnomAD4 genome AF: 0.0129 AC: 1960 AN: 152294 Hom.: 91 Cov.: 32 AF XY: 0.0142 AC XY: 1058 AN XY: 74460

Gnomad4 AFR AF: 0.00221

Gnomad4 AMR AF: 0.0893

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00604

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00846 Hom.: 1

Bravo AF: 0.0180

Asia WGS AF: 0.00577 AC: 20 AN: 3478

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

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.11
DANN	Benign	0.55

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: rs28925905; hg19: chr4-144360908;