rs7663712

chr4-143339964-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.72+2704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 152,312 control chromosomes in the GnomAD database, including 179 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 0.046 (179 hom., cov: 33)
• Consequence: GAB1 NM_002039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAB1	NM_002039.4	c.72+2704A>G		intron_variant		ENST00000262994.9
GAB1	NM_207123.3	c.72+2704A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAB1	ENST00000262994.9	c.72+2704A>G		intron_variant		1	NM_002039.4	A1
GAB1	ENST00000262995.9	c.72+2704A>G		intron_variant		1		P3
GAB1	ENST00000514639.5	c.72+2704A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6970 AN: 152194 Hom.: 179 Cov.: 33

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0458 AC: 6980 AN: 152312 Hom.: 179 Cov.: 33 AF XY: 0.0444 AC XY: 3305 AN XY: 74490

Gnomad4 AFR AF: 0.0464

Gnomad4 AMR AF: 0.0428

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.0545

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0529

Gnomad4 OTH AF: 0.0483

Alfa AF: 0.0515 Hom.: 44

Bravo AF: 0.0463

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	6.1
Dann	Benign	0.63

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: rs7663712; hg19: chr4-144261117;