3-14514303-A-G

Position:

• chr3-14514303-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080423.4(GRIP2):​c.1482T>C​(p.Ser494=) variant causes a synonymous change. The variant allele was found at a frequency of 0.566 in 1,560,482 control chromosomes in the GnomAD database, including 253,336 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 0.58 (25438 hom., cov: 29)
  • Exomes 𝑓: 0.56 (227898 hom.)
• Consequence: GRIP2 NM_001080423.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01

Genes affected

GRIP2 (HGNC:23841): (glutamate receptor interacting protein 2) Predicted to enable protein C-terminus binding activity. Predicted to be involved in several processes, including neurotransmitter receptor transport, endosome to postsynaptic membrane; positive regulation of AMPA glutamate receptor clustering; and positive regulation of excitatory postsynaptic potential. Predicted to act upstream of or within Notch signaling pathway; artery smooth muscle contraction; and positive regulation of blood pressure. Predicted to be located in cytoplasm; dendritic shaft; and neuron spine. Predicted to be active in glutamatergic synapse and postsynaptic density. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIP2	NM_001080423.4	c.1482T>C	p.Ser494=	synonymous_variant	12/24	ENST00000621039.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIP2	ENST00000621039.5	c.1482T>C	p.Ser494=	synonymous_variant	12/24	1	NM_001080423.4	P2
GRIP2	ENST00000619221.4	c.1773T>C	p.Ser591=	synonymous_variant	13/25	5
GRIP2	ENST00000637182.1	c.1497T>C	p.Ser499=	synonymous_variant	12/24	5		A1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87315 AN: 151070 Hom.: 25415 Cov.: 29

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.606

GnomAD3 exomes AF: 0.591 AC: 99786 AN: 168734 Hom.: 30254 AF XY: 0.591 AC XY: 53286 AN XY: 90126

Gnomad AFR exome AF: 0.568

Gnomad AMR exome AF: 0.689

Gnomad ASJ exome AF: 0.518

Gnomad EAS exome AF: 0.749

Gnomad SAS exome AF: 0.689

Gnomad FIN exome AF: 0.467

Gnomad NFE exome AF: 0.536

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.565 AC: 795793 AN: 1409294 Hom.: 227898 Cov.: 47 AF XY: 0.568 AC XY: 395442 AN XY: 696106

Gnomad4 AFR exome AF: 0.589

Gnomad4 AMR exome AF: 0.686

Gnomad4 ASJ exome AF: 0.512

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.578 AC: 87382 AN: 151188 Hom.: 25438 Cov.: 29 AF XY: 0.578 AC XY: 42689 AN XY: 73836

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.604

Alfa AF: 0.566 Hom.: 43159

Bravo AF: 0.592

Asia WGS AF: 0.737 AC: 2565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.9
DANN	Benign	0.82

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: rs4613440; hg19: chr3-14555811;