12-66591446-A-G

Variant names:

• chr12-66591446-A-G
• rs12314237
• NM_001366722.1:c.136+5401T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366722.1(GRIP1):​c.136+5401T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,904 control chromosomes in the GnomAD database, including 4,858 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 0.25 (4858 hom., cov: 31)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 0 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	NM_001366722.1	MANE Select	c.136+5401T>C		intron	N/A	NP_001353651.1
	GRIP1	NM_001379345.1		c.214+5401T>C		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.139+5401T>C		intron	N/A	NP_001426251.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000359742.9	TSL:5 MANE Select	c.136+5401T>C		intron	N/A	ENSP00000352780.4
	GRIP1	ENST00000398016.7	TSL:1	c.136+5401T>C		intron	N/A	ENSP00000381098.3
	GRIP1	ENST00000696989.1		c.361+5401T>C		intron	N/A	ENSP00000513025.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37899 AN: 151786 Hom.: 4849 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.250 AC: 37932 AN: 151904 Hom.: 4858 Cov.: 31 AF XY: 0.250 AC XY: 18535 AN XY: 74244

African (AFR) AF: 0.236 AC: 9765 AN: 41374

American (AMR) AF: 0.279 AC: 4263 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3470

East Asian (EAS) AF: 0.215 AC: 1106 AN: 5134

South Asian (SAS) AF: 0.211 AC: 1012 AN: 4804

European-Finnish (FIN) AF: 0.257 AC: 2723 AN: 10584

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17396 AN: 67956

Other (OTH) AF: 0.263 AC: 555 AN: 2112

Alfa AF: 0.254 Hom.: 2824

Bravo AF: 0.249

Asia WGS AF: 0.225 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.32
PhyloP100		-0.37
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: rs12314237; hg19: chr12-66985226;