rs13277

Variant names:

• chr12-66392311-G-C
• rs13277
• NM_001366722.1:c.2461C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-66392311-G-C
• chr12-66392311-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366722.1(GRIP1):​c.2461C>G​(p.Gln821Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.972 in 1,587,370 control chromosomes in the GnomAD database, including 755,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (61226 hom., cov: 32)
  • Exomes 𝑓: 0.98 (694649 hom.)
• Consequence: GRIP1 NM_001366722.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 7.63
• Publications: 26 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Fraser syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.574098E-7).
• BP6: Variant 12-66392311-G-C is Benign according to our data. Variant chr12-66392311-G-C is described in ClinVar as Benign. ClinVar VariationId is 261410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366722.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	NM_001366722.1	MANE Select	c.2461C>G	p.Gln821Glu	missense	Exon 19 of 25	NP_001353651.1	Q9Y3R0-1
	GRIP1	NM_001379345.1		c.2539C>G	p.Gln847Glu	missense	Exon 19 of 25	NP_001366274.1
	GRIP1	NM_001439322.1		c.2464C>G	p.Gln822Glu	missense	Exon 19 of 24	NP_001426251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000359742.9	TSL:5 MANE Select	c.2461C>G	p.Gln821Glu	missense	Exon 19 of 25	ENSP00000352780.4	Q9Y3R0-1
	GRIP1	ENST00000398016.7	TSL:1	c.2305C>G	p.Gln769Glu	missense	Exon 18 of 24	ENSP00000381098.3	Q9Y3R0-3
	GRIP1	ENST00000536215.5	TSL:1	c.1981C>G	p.Gln661Glu	missense	Exon 16 of 19	ENSP00000446011.1	F5H4Q7

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134343 AN: 152090 Hom.: 61211 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.990

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.914

GnomAD2 exomes AF: 0.951 AC: 237058 AN: 249228 AF XY: 0.962

Gnomad AFR exome AF: 0.626

Gnomad AMR exome AF: 0.861

Gnomad ASJ exome AF: 0.995

Gnomad EAS exome AF: 0.949

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.998

Gnomad OTH exome AF: 0.969

GnomAD4 exome AF: 0.982 AC: 1409044 AN: 1435162 Hom.: 694649 Cov.: 26 AF XY: 0.984 AC XY: 704320 AN XY: 715744

African (AFR) AF: 0.628 AC: 20724 AN: 32978

American (AMR) AF: 0.864 AC: 38590 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 25848 AN: 25966

East Asian (EAS) AF: 0.901 AC: 35658 AN: 39576

South Asian (SAS) AF: 0.993 AC: 85095 AN: 85710

European-Finnish (FIN) AF: 1.00 AC: 53404 AN: 53410

Middle Eastern (MID) AF: 0.978 AC: 5594 AN: 5722

European-Non Finnish (NFE) AF: 0.999 AC: 1086647 AN: 1087638

Other (OTH) AF: 0.967 AC: 57484 AN: 59472

GnomAD4 genome AF: 0.883 AC: 134402 AN: 152208 Hom.: 61226 Cov.: 32 AF XY: 0.885 AC XY: 65872 AN XY: 74416

African (AFR) AF: 0.636 AC: 26366 AN: 41470

American (AMR) AF: 0.870 AC: 13308 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3454 AN: 3472

East Asian (EAS) AF: 0.937 AC: 4832 AN: 5158

South Asian (SAS) AF: 0.990 AC: 4780 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10625 AN: 10626

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67904 AN: 68036

Other (OTH) AF: 0.915 AC: 1934 AN: 2114

Alfa AF: 0.980 Hom.: 55370

Bravo AF: 0.862

TwinsUK AF: 0.999 AC: 3706

ALSPAC AF: 0.999 AC: 3851

ESP6500AA AF: 0.669 AC: 2717

ESP6500EA AF: 0.997 AC: 8312

ExAC AF: 0.949 AC: 114719

Asia WGS AF: 0.940 AC: 3270 AN: 3478

EpiCase AF: 0.997

EpiControl AF: 0.998

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Fraser syndrome 1 (3)
-	-	3	not provided (3)
-	-	2	Fraser syndrome 3 (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.70
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	8.6e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.6
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.36
Sift	Benign	0.33	T
Sift4G	Benign	1.0	T
Polyphen		0.49	P
Vest4		0.28
MPC		0.32
ClinPred		0.056	T
GERP RS		4.5
Varity_R		0.13
gMVP		0.41
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs13277; hg19: chr12-66786091; COSMIC: COSV107266243; COSMIC: COSV107266243;