12-66813284-A-G

Variant names:

• chr12-66813284-A-G
• rs11176432
• NM_001439322.1:c.59-216357T>C

Variant summary

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

The NM_001439322.1(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_001439322.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -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.

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.59-216357T>C		intron	N/A	NP_001426251.1
	GRIP1	NM_001439323.1		c.59-216357T>C		intron	N/A	NP_001426252.1
	GRIP1	NM_001379349.1		c.59-216357T>C		intron	N/A	NP_001366278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000643019.1		c.59-216357T>C		intron	N/A	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

African (AFR) AF: 0.284 AC: 11773 AN: 41438

American (AMR) AF: 0.552 AC: 8430 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3466

East Asian (EAS) AF: 0.545 AC: 2782 AN: 5100

South Asian (SAS) AF: 0.533 AC: 2560 AN: 4800

European-Finnish (FIN) AF: 0.440 AC: 4646 AN: 10562

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33930 AN: 67944

Other (OTH) AF: 0.499 AC: 1050 AN: 2106

Alfa AF: 0.489 Hom.: 25426

Bravo AF: 0.449

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.67
DANN	Benign	0.44
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs11176432; hg19: chr12-67207064;