rs7970076

Variant names:

• chr12-66392293-A-G
• rs7970076
• NM_001366722.1:c.2464+15T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-66392293-A-G
• chr12-66392293-A-C
• chr12-66392293-A-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.2464+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,490,130 control chromosomes in the GnomAD database, including 739,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73411 hom., cov: 32)
  • Exomes 𝑓: 1.0 (666106 hom.)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.696
• Publications: 7 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=-0.9).
• BP6: Variant 12-66392293-A-G is Benign according to our data. Variant chr12-66392293-A-G is described in ClinVar as Benign. ClinVar VariationId is 261411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.2464+15T>C		intron	N/A	NP_001353651.1	Q9Y3R0-1
	GRIP1	NM_001379345.1		c.2542+15T>C		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.2467+15T>C		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.2464+15T>C		intron	N/A	ENSP00000352780.4	Q9Y3R0-1
	GRIP1	ENST00000398016.7	TSL:1	c.2308+15T>C		intron	N/A	ENSP00000381098.3	Q9Y3R0-3
	GRIP1	ENST00000536215.5	TSL:1	c.1984+15T>C		intron	N/A	ENSP00000446011.1	F5H4Q7

Frequencies

GnomAD3 genomes AF: 0.981 AC: 149372 AN: 152218 Hom.: 73364 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.989

GnomAD2 exomes AF: 0.995 AC: 247674 AN: 248954 AF XY: 0.996

Gnomad AFR exome AF: 0.929

Gnomad AMR exome AF: 0.996

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome AF: 0.998 AC: 1334924 AN: 1337794 Hom.: 666106 Cov.: 21 AF XY: 0.998 AC XY: 671339 AN XY: 672550

African (AFR) AF: 0.932 AC: 29492 AN: 31642

American (AMR) AF: 0.996 AC: 44388 AN: 44582

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25358 AN: 25358

East Asian (EAS) AF: 1.00 AC: 39182 AN: 39186

South Asian (SAS) AF: 1.00 AC: 83751 AN: 83764

European-Finnish (FIN) AF: 1.00 AC: 53332 AN: 53344

Middle Eastern (MID) AF: 0.998 AC: 5542 AN: 5554

European-Non Finnish (NFE) AF: 1.00 AC: 997842 AN: 998018

Other (OTH) AF: 0.995 AC: 56037 AN: 56346

GnomAD4 genome AF: 0.981 AC: 149479 AN: 152336 Hom.: 73411 Cov.: 32 AF XY: 0.982 AC XY: 73163 AN XY: 74484

African (AFR) AF: 0.935 AC: 38878 AN: 41570

American (AMR) AF: 0.992 AC: 15194 AN: 15310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 1.00 AC: 4825 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10627 AN: 10628

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68017 AN: 68038

Other (OTH) AF: 0.989 AC: 2088 AN: 2112

Alfa AF: 0.987 Hom.: 21416

Bravo AF: 0.978

Asia WGS AF: 0.996 AC: 3463 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.39
PhyloP100		-0.70
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: rs7970076; hg19: chr12-66786073;