4-143337239-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_002039.4(GAB1):c.51G>C(p.Pro17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000678 in 1,583,246 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (4 hom.)
• Consequence: GAB1 NM_002039.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.06

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]

LOC124900789 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 4-143337239-G-C is Benign according to our data. Variant chr4-143337239-G-C is described in ClinVar as [Benign]. Clinvar id is 3052380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.06 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAB1	NM_002039.4	c.51G>C	p.Pro17=	synonymous_variant	1/10	ENST00000262994.9
GAB1	NM_207123.3	c.51G>C	p.Pro17=	synonymous_variant	1/11
LOC124900789	XR_007058287.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAB1	ENST00000262994.9	c.51G>C	p.Pro17=	synonymous_variant	1/10	1	NM_002039.4	A1
GAB1	ENST00000262995.9	c.51G>C	p.Pro17=	synonymous_variant	1/11	1		P3
GAB1	ENST00000514639.5	c.51G>C	p.Pro17=	synonymous_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.00349 AC: 531 AN: 152150 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000959 AC: 190 AN: 198064 Hom.: 2 AF XY: 0.000832 AC XY: 88 AN XY: 105824

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.00123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00178

GnomAD4 exome AF: 0.000379 AC: 542 AN: 1430980 Hom.: 4 Cov.: 30 AF XY: 0.000340 AC XY: 241 AN XY: 708494

Gnomad4 AFR exome AF: 0.0128

Gnomad4 AMR exome AF: 0.00111

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000164

Gnomad4 OTH exome AF: 0.000845

GnomAD4 genome AF: 0.00349 AC: 532 AN: 152266 Hom.: 3 Cov.: 32 AF XY: 0.00371 AC XY: 276 AN XY: 74442

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000982 Hom.: 1

Bravo AF: 0.00397

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

GAB1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	15
Dann	Benign	0.91

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: rs147010310; hg19: chr4-144258392;