rs10506506

Variant names:

• chr12-66841387-G-A
• rs10506506
• NM_001439322.1:c.58+227663C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-66841387-G-A
• chr12-66841387-G-C
• chr12-66841387-G-T

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+227663C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,084 control chromosomes in the GnomAD database, including 2,145 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 0.16 (2145 hom., cov: 32)
• Consequence: GRIP1 NM_001439322.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP1	NM_001439322.1	c.58+227663C>T		intron_variant	Intron 1 of 23		NP_001426251.1
GRIP1	NM_001439323.1	c.58+227663C>T		intron_variant	Intron 1 of 23		NP_001426252.1
GRIP1	NM_001379349.1	c.58+227663C>T		intron_variant	Intron 1 of 23		NP_001366278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000643019.1	c.58+227663C>T		intron_variant	Intron 1 of 1			ENSP00000495444.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24589 AN: 151966 Hom.: 2140 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.162 AC: 24600 AN: 152084 Hom.: 2145 Cov.: 32 AF XY: 0.163 AC XY: 12135 AN XY: 74322

African (AFR) AF: 0.136 AC: 5661 AN: 41490

American (AMR) AF: 0.166 AC: 2534 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3470

East Asian (EAS) AF: 0.374 AC: 1931 AN: 5166

South Asian (SAS) AF: 0.279 AC: 1345 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1595 AN: 10576

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.149 AC: 10119 AN: 67990

Other (OTH) AF: 0.190 AC: 403 AN: 2116

Alfa AF: 0.147 Hom.: 274

Bravo AF: 0.162

Asia WGS AF: 0.310 AC: 1076 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.19
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs10506506; hg19: chr12-67235167;