3-14514303-A-G

Variant names:

• chr3-14514303-A-G
• rs4613440
• NM_001080423.4:c.1482T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080423.4(GRIP2):​c.1482T>C​(p.Ser494Ser) 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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080423.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP2	NM_001080423.4	MANE Select	c.1482T>C	p.Ser494Ser	synonymous	Exon 12 of 24	NP_001073892.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP2	ENST00000621039.5	TSL:1 MANE Select	c.1482T>C	p.Ser494Ser	synonymous	Exon 12 of 24	ENSP00000478352.1
	GRIP2	ENST00000619221.4	TSL:5	c.1773T>C	p.Ser591Ser	synonymous	Exon 13 of 25	ENSP00000480660.1
	GRIP2	ENST00000637182.1	TSL:5	c.1497T>C	p.Ser499Ser	synonymous	Exon 12 of 24	ENSP00000490949.1

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

GnomAD2 exomes AF: 0.591 AC: 99786 AN: 168734 AF XY: 0.591

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 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

African (AFR) AF: 0.589 AC: 18950 AN: 32194

American (AMR) AF: 0.686 AC: 25303 AN: 36872

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 12852 AN: 25116

East Asian (EAS) AF: 0.800 AC: 29240 AN: 36564

South Asian (SAS) AF: 0.689 AC: 54883 AN: 79634

European-Finnish (FIN) AF: 0.466 AC: 23030 AN: 49450

Middle Eastern (MID) AF: 0.678 AC: 3749 AN: 5532

European-Non Finnish (NFE) AF: 0.547 AC: 593945 AN: 1085398

Other (OTH) AF: 0.578 AC: 33841 AN: 58534

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

African (AFR) AF: 0.593 AC: 24368 AN: 41122

American (AMR) AF: 0.644 AC: 9808 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1781 AN: 3460

East Asian (EAS) AF: 0.768 AC: 3919 AN: 5102

South Asian (SAS) AF: 0.701 AC: 3366 AN: 4802

European-Finnish (FIN) AF: 0.457 AC: 4745 AN: 10380

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37362 AN: 67816

Other (OTH) AF: 0.604 AC: 1257 AN: 2080

Alfa AF: 0.568 Hom.: 60588

Bravo AF: 0.592

Asia WGS AF: 0.737 AC: 2565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.9
DANN	Benign	0.82
PhyloP100		4.0

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

Other links and lift over

dbSNP: rs4613440; hg19: chr3-14555811; COSMIC: COSV99817103; COSMIC: COSV99817103;