3-14534560-C-T

Variant names:

• chr3-14534560-C-T
• rs6442460
• NM_001080423.4:c.40+5709G>A

Variant summary

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

The NM_001080423.4(GRIP2):​c.40+5709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,094 control chromosomes in the GnomAD database, including 67,867 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 0.94 (67867 hom., cov: 30)
• Consequence: GRIP2 NM_001080423.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 1 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=-0.32).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP2	NM_001080423.4	c.40+5709G>A		intron_variant	Intron 1 of 23	ENST00000621039.5	NP_001073892.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIP2	ENST00000621039.5	c.40+5709G>A		intron_variant	Intron 1 of 23	1	NM_001080423.4	ENSP00000478352.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143449 AN: 151976 Hom.: 67804 Cov.: 30

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.944 AC: 143570 AN: 152094 Hom.: 67867 Cov.: 30 AF XY: 0.943 AC XY: 70114 AN XY: 74320

African (AFR) AF: 0.986 AC: 40944 AN: 41524

American (AMR) AF: 0.970 AC: 14825 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3150 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5168

South Asian (SAS) AF: 0.976 AC: 4702 AN: 4816

European-Finnish (FIN) AF: 0.869 AC: 9152 AN: 10534

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.919 AC: 62451 AN: 67978

Other (OTH) AF: 0.957 AC: 2020 AN: 2110

Alfa AF: 0.929 Hom.: 109618

Bravo AF: 0.953

Asia WGS AF: 0.988 AC: 3434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.90
PhyloP100		2.2

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: rs6442460; hg19: chr3-14576067;