rs2904532

Positions:

• chr12-66902264-A-G

Variant summary

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

The XR_007063353.1(LOC124902956):​n.20681T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,096 control chromosomes in the GnomAD database, including 5,532 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 0.26 (5532 hom., cov: 32)
• Consequence: LOC124902956 XR_007063353.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386

Genes affected

LOC124902956 (HGNC:):

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124902956	XR_007063353.1	n.20681T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000643019.1	c.58+166786T>C		intron_variant				ENSP00000495444
GRIP1	ENST00000535721.1	n.114-10310T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39435 AN: 151978 Hom.: 5515 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.259 AC: 39464 AN: 152096 Hom.: 5532 Cov.: 32 AF XY: 0.268 AC XY: 19919 AN XY: 74356

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.235

Alfa AF: 0.258 Hom.: 893

Bravo AF: 0.242

Asia WGS AF: 0.353 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.2
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2904532; hg19: chr12-67296044;