12-66767867-T-C

Position:

• chr12-66767867-T-C

Variant summary

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

The NM_001379345.1(GRIP1):​c.133+36186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 152,234 control chromosomes in the GnomAD database, including 640 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 0.081 (640 hom., cov: 32)
• Consequence: GRIP1 NM_001379345.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIP1	NM_001366723.1	c.133+36186A>G		intron_variant
GRIP1	NM_001366724.1	c.133+36186A>G		intron_variant
GRIP1	NM_001379345.1	c.133+36186A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIP1	ENST00000538373.1	c.-420+36186A>G		intron_variant		4
GRIP1	ENST00000539540.5	c.-114+36065A>G		intron_variant		5
GRIP1	ENST00000540433.5	c.-33+36065A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12357 AN: 152116 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0813 AC: 12377 AN: 152234 Hom.: 640 Cov.: 32 AF XY: 0.0812 AC XY: 6047 AN XY: 74438

Gnomad4 AFR AF: 0.0888

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0995

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0598

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0709 Hom.: 557

Bravo AF: 0.0952

Asia WGS AF: 0.144 AC: 500 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11176419; hg19: chr12-67161647;