12-67019317-G-T

Position:

• chr12-67019317-G-T

Variant summary

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

The NM_001379349.1(GRIP1):​c.58+49733C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,174 control chromosomes in the GnomAD database, including 1,307 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 0.11 (1307 hom., cov: 32)
• Consequence: GRIP1 NM_001379349.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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]

GRIP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIP1	NM_001379349.1	c.58+49733C>A		intron_variant			NP_001366278.1
GRIP1	NM_001379351.1	c.58+49733C>A		intron_variant			NP_001366280.1
GRIP1	XM_005268754.5	c.58+49733C>A		intron_variant			XP_005268811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000643019.1	c.58+49733C>A		intron_variant				ENSP00000495444.1
GRIP1	ENST00000535721.1	n.113+49733C>A		intron_variant		3
ENSG00000257083	ENST00000652412.1	n.516-55152C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17255 AN: 152056 Hom.: 1291 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.114 AC: 17294 AN: 152174 Hom.: 1307 Cov.: 32 AF XY: 0.118 AC XY: 8800 AN XY: 74374

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0763 Hom.: 130

Bravo AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10506540; hg19: chr12-67413097;