chr12-66347717-G-GTGA

Position:

• chr12-66347717-G-GTGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001366722.1(GRIP1):​c.*1301_*1302insTCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00956 in 151,606 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0096 (22 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: GRIP1 NM_001366722.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.22

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-66347717-G-GTGA is Benign according to our data. Variant chr12-66347717-G-GTGA is described in ClinVar as [Likely_benign]. Clinvar id is 310273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00956 (1449/151606) while in subpopulation AFR AF= 0.0339 (1400/41318). AF 95% confidence interval is 0.0324. There are 22 homozygotes in gnomad4. There are 693 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIP1	NM_001366722.1	c.*1301_*1302insTCA		3_prime_UTR_variant	25/25	ENST00000359742.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIP1	ENST00000359742.9	c.*1301_*1302insTCA		3_prime_UTR_variant	25/25	5	NM_001366722.1	P1
GRIP1	ENST00000398016.7	c.*1301_*1302insTCA		3_prime_UTR_variant	24/24	1
GRIP1	ENST00000696989.1	c.*1301_*1302insTCA		3_prime_UTR_variant	23/23

Frequencies

GnomAD3 genomes AF: 0.00955 AC: 1446 AN: 151492 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00211

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00672

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.00956 AC: 1449 AN: 151606 Hom.: 22 Cov.: 33 AF XY: 0.00936 AC XY: 693 AN XY: 74050

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.00211

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00666

Alfa AF: 0.00733 Hom.: 0

Bravo AF: 0.0107

Asia WGS AF: 0.00116 AC: 4 AN: 3458

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fraser syndrome 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200995788; hg19: chr12-66741497;