12-67019317-G-T

Variant names:

• chr12-67019317-G-T
• rs10506540
• NM_001439322.1:c.58+49733C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001439322.1(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_001439322.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Fraser syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• Fraser syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000257083 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001439322.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	NM_001439322.1		c.58+49733C>A		intron	N/A	NP_001426251.1
	GRIP1	NM_001439323.1		c.58+49733C>A		intron	N/A	NP_001426252.1
	GRIP1	NM_001379349.1		c.58+49733C>A		intron	N/A	NP_001366278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000643019.1		c.58+49733C>A		intron	N/A	ENSP00000495444.1
	GRIP1	ENST00000535721.1	TSL:3	n.113+49733C>A		intron	N/A
	ENSG00000257083	ENST00000652412.1		n.516-55152C>A		intron	N/A

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

African (AFR) AF: 0.0256 AC: 1066 AN: 41560

American (AMR) AF: 0.167 AC: 2555 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 456 AN: 3464

East Asian (EAS) AF: 0.263 AC: 1353 AN: 5152

South Asian (SAS) AF: 0.182 AC: 878 AN: 4812

European-Finnish (FIN) AF: 0.171 AC: 1812 AN: 10580

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8688 AN: 68016

Other (OTH) AF: 0.126 AC: 266 AN: 2110

Alfa AF: 0.107 Hom.: 395

Bravo AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.63
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs10506540; hg19: chr12-67413097;