rs12316942

Variant names:

• chr12-66515609-C-T
• rs12316942
• NM_001366722.1:c.724+10G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-66515609-C-T
• chr12-66515609-C-G

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.724+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,609,018 control chromosomes in the GnomAD database, including 328,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35396 hom., cov: 31)
  • Exomes 𝑓: 0.63 (292970 hom.)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0320
• 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=-0.9).
• BP6: Variant 12-66515609-C-T is Benign according to our data. Variant chr12-66515609-C-T is described in ClinVar as Benign. ClinVar VariationId is 261413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 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.724+10G>A		intron	N/A	NP_001353651.1	Q9Y3R0-1
	GRIP1	NM_001379345.1		c.802+10G>A		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.727+10G>A		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.724+10G>A		intron	N/A	ENSP00000352780.4	Q9Y3R0-1
	GRIP1	ENST00000398016.7	TSL:1	c.724+10G>A		intron	N/A	ENSP00000381098.3	Q9Y3R0-3
	GRIP1	ENST00000536215.5	TSL:1	c.556+10G>A		intron	N/A	ENSP00000446011.1	F5H4Q7

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102876 AN: 151884 Hom.: 35363 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.721

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.668

GnomAD2 exomes AF: 0.647 AC: 161390 AN: 249430 AF XY: 0.650

Gnomad AFR exome AF: 0.805

Gnomad AMR exome AF: 0.628

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.647

Gnomad FIN exome AF: 0.577

Gnomad NFE exome AF: 0.617

Gnomad OTH exome AF: 0.648

GnomAD4 exome AF: 0.632 AC: 920881 AN: 1457016 Hom.: 292970 Cov.: 34 AF XY: 0.635 AC XY: 460648 AN XY: 725196

African (AFR) AF: 0.808 AC: 26994 AN: 33390

American (AMR) AF: 0.633 AC: 28305 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 16994 AN: 26076

East Asian (EAS) AF: 0.676 AC: 26819 AN: 39670

South Asian (SAS) AF: 0.748 AC: 64451 AN: 86142

European-Finnish (FIN) AF: 0.581 AC: 31010 AN: 53394

Middle Eastern (MID) AF: 0.707 AC: 4067 AN: 5754

European-Non Finnish (NFE) AF: 0.617 AC: 683300 AN: 1107674

Other (OTH) AF: 0.647 AC: 38941 AN: 60210

GnomAD4 genome AF: 0.677 AC: 102968 AN: 152002 Hom.: 35396 Cov.: 31 AF XY: 0.678 AC XY: 50382 AN XY: 74276

African (AFR) AF: 0.801 AC: 33216 AN: 41484

American (AMR) AF: 0.675 AC: 10294 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3470

East Asian (EAS) AF: 0.651 AC: 3355 AN: 5152

South Asian (SAS) AF: 0.747 AC: 3602 AN: 4820

European-Finnish (FIN) AF: 0.575 AC: 6067 AN: 10556

Middle Eastern (MID) AF: 0.707 AC: 205 AN: 290

European-Non Finnish (NFE) AF: 0.617 AC: 41917 AN: 67952

Other (OTH) AF: 0.669 AC: 1411 AN: 2108

Alfa AF: 0.644 Hom.: 53516

Bravo AF: 0.685

Asia WGS AF: 0.712 AC: 2480 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	-0.90
CADD	Benign	0.30
DANN	Benign	0.27
PhyloP100		-0.032
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12316942; hg19: chr12-66909389;