12-66813284-A-G

Position:

• chr12-66813284-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379349.1(GRIP1):​c.59-216357T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,868 control chromosomes in the GnomAD database, including 15,989 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 0.45 (15989 hom., cov: 30)
• Consequence: GRIP1 NM_001379349.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

Genes affected

GRIP1 (HGNC:18708): (glutamate receptor interacting protein 1) This gene encodes a member of the glutamate receptor interacting protein family. The encoded scaffold protein binds to and mediates the trafficking and membrane organization of a number of transmembrane proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIP1	NM_001379349.1	c.59-216357T>C		intron_variant			NP_001366278.1
GRIP1	NM_001379351.1	c.59-216357T>C		intron_variant			NP_001366280.1
GRIP1	XM_005268754.5	c.59-216357T>C		intron_variant			XP_005268811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000643019.1	c.59-216357T>C		intron_variant				ENSP00000495444.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67759 AN: 151750 Hom.: 15981 Cov.: 30

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.446 AC: 67785 AN: 151868 Hom.: 15989 Cov.: 30 AF XY: 0.449 AC XY: 33284 AN XY: 74184

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.499

Alfa AF: 0.495 Hom.: 17046

Bravo AF: 0.449

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.67
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11176432; hg19: chr12-67207064;