rs7397862

Variant names:

• chr12-66420707-C-A
• rs7397862
• NM_001366722.1:c.1838+13G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-66420707-C-A
• chr12-66420707-C-G
• chr12-66420707-C-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.1838+13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,429,348 control chromosomes in the GnomAD database, including 253,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (21439 hom., cov: 31)
  • Exomes 𝑓: 0.60 (232256 hom.)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.268
• Publications: 10 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 (BayesDel_noAF=-0.84).
• BP6: Variant 12-66420707-C-A is Benign according to our data. Variant chr12-66420707-C-A is described in ClinVar as Benign. ClinVar VariationId is 261409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 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.1838+13G>T		intron	N/A	NP_001353651.1	Q9Y3R0-1
	GRIP1	NM_001379345.1		c.1916+13G>T		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.1841+13G>T		intron	N/A	NP_001426251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000359742.9	TSL:5 MANE Select	c.1838+13G>T		intron	N/A	ENSP00000352780.4	Q9Y3R0-1
	GRIP1	ENST00000398016.7	TSL:1	c.1682+13G>T		intron	N/A	ENSP00000381098.3	Q9Y3R0-3
	GRIP1	ENST00000536215.5	TSL:1	c.1358+13G>T		intron	N/A	ENSP00000446011.1	F5H4Q7

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76414 AN: 151842 Hom.: 21430 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.534

GnomAD2 exomes AF: 0.565 AC: 140688 AN: 249078 AF XY: 0.574

Gnomad AFR exome AF: 0.245

Gnomad AMR exome AF: 0.528

Gnomad ASJ exome AF: 0.620

Gnomad EAS exome AF: 0.349

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.630

Gnomad OTH exome AF: 0.576

GnomAD4 exome AF: 0.596 AC: 761429 AN: 1277388 Hom.: 232256 Cov.: 19 AF XY: 0.598 AC XY: 385800 AN XY: 645368

African (AFR) AF: 0.237 AC: 7245 AN: 30566

American (AMR) AF: 0.530 AC: 23538 AN: 44418

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 15400 AN: 24966

East Asian (EAS) AF: 0.317 AC: 12358 AN: 38942

South Asian (SAS) AF: 0.573 AC: 47281 AN: 82576

European-Finnish (FIN) AF: 0.651 AC: 34616 AN: 53182

Middle Eastern (MID) AF: 0.564 AC: 3074 AN: 5450

European-Non Finnish (NFE) AF: 0.622 AC: 586934 AN: 943004

Other (OTH) AF: 0.571 AC: 30983 AN: 54284

GnomAD4 genome AF: 0.503 AC: 76453 AN: 151960 Hom.: 21439 Cov.: 31 AF XY: 0.504 AC XY: 37437 AN XY: 74242

African (AFR) AF: 0.251 AC: 10380 AN: 41434

American (AMR) AF: 0.508 AC: 7754 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2135 AN: 3470

East Asian (EAS) AF: 0.328 AC: 1691 AN: 5152

South Asian (SAS) AF: 0.560 AC: 2695 AN: 4816

European-Finnish (FIN) AF: 0.652 AC: 6872 AN: 10542

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42960 AN: 67960

Other (OTH) AF: 0.535 AC: 1133 AN: 2116

Alfa AF: 0.570 Hom.: 5285

Bravo AF: 0.479

Asia WGS AF: 0.435 AC: 1514 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.26
PhyloP100		-0.27
Mutation Taster		=100/0	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: rs7397862; hg19: chr12-66814487; COSMIC: COSV54024696;