12-66971260-C-T

Variant names:

• chr12-66971260-C-T
• rs1021868
• NM_001439322.1:c.58+97790G>A

Variant summary

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

The NM_001439322.1(GRIP1):​c.58+97790G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,978 control chromosomes in the GnomAD database, including 4,183 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 0.22 (4183 hom., cov: 32)
• Consequence: GRIP1 NM_001439322.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 3 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

ENSG00000257083 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP1	NM_001439322.1	c.58+97790G>A		intron_variant	Intron 1 of 23		NP_001426251.1
GRIP1	NM_001439323.1	c.58+97790G>A		intron_variant	Intron 1 of 23		NP_001426252.1
GRIP1	NM_001379349.1	c.58+97790G>A		intron_variant	Intron 1 of 23		NP_001366278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000643019.1	c.58+97790G>A		intron_variant	Intron 1 of 1			ENSP00000495444.1
GRIP1	ENST00000535721.1	n.114-79306G>A		intron_variant	Intron 1 of 1	3
ENSG00000257083	ENST00000652412.1	n.516-7095G>A		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33835 AN: 151860 Hom.: 4175 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.223 AC: 33869 AN: 151978 Hom.: 4183 Cov.: 32 AF XY: 0.231 AC XY: 17129 AN XY: 74266

African (AFR) AF: 0.127 AC: 5258 AN: 41420

American (AMR) AF: 0.241 AC: 3680 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3466

East Asian (EAS) AF: 0.249 AC: 1287 AN: 5162

South Asian (SAS) AF: 0.244 AC: 1174 AN: 4812

European-Finnish (FIN) AF: 0.352 AC: 3712 AN: 10548

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17319 AN: 67970

Other (OTH) AF: 0.194 AC: 411 AN: 2116

Alfa AF: 0.153 Hom.: 342

Bravo AF: 0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.038
DANN	Benign	0.27
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs1021868; hg19: chr12-67365040;