rs2904532

Variant names:

• chr12-66902264-A-G
• rs2904532
• ENST00000787658.1:n.622T>C

Variant summary

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

The ENST00000787658.1(ENSG00000302533):​n.622T>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: ENSG00000302533 ENST00000787658.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386
• Publications: 5 publications found

Genes affected

ENSG00000302533 (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]

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=-0.93).
• 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 rank	MANE	Protein	UniProt
LOC124902956	XR_007063353.1	n.20681T>C		non_coding_transcript_exon_variant	Exon 2 of 2
GRIP1	NM_001439322.1	c.58+166786T>C		intron_variant	Intron 1 of 23		NP_001426251.1
GRIP1	NM_001439323.1	c.58+166786T>C		intron_variant	Intron 1 of 23		NP_001426252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000302533	ENST00000787658.1	n.622T>C		non_coding_transcript_exon_variant	Exon 3 of 3
ENSG00000302533	ENST00000787659.1	n.540T>C		non_coding_transcript_exon_variant	Exon 3 of 3
ENSG00000302533	ENST00000787660.1	n.698T>C		non_coding_transcript_exon_variant	Exon 4 of 4

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

African (AFR) AF: 0.172 AC: 7149 AN: 41508

American (AMR) AF: 0.210 AC: 3214 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2325 AN: 5162

South Asian (SAS) AF: 0.346 AC: 1671 AN: 4824

European-Finnish (FIN) AF: 0.368 AC: 3888 AN: 10558

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19573 AN: 67976

Other (OTH) AF: 0.235 AC: 496 AN: 2110

Alfa AF: 0.255 Hom.: 903

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
PhyloP100		0.39

Splicing

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

Other links and lift over

dbSNP: rs2904532; hg19: chr12-67296044;