17-38326103-C-T

Variant names:

• chr17-38326103-C-T
• rs4794777
• NM_001004334.4:c.*362G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001004334.4(GPR179):​c.*362G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 229,972 control chromosomes in the GnomAD database, including 589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (559 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (30 hom.)
• Consequence: GPR179 NM_001004334.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.171

Genes affected

GPR179 (HGNC:31371): (G protein-coupled receptor 179) This gene encodes a member of the glutamate receptor subfamily of G protein-coupled receptors. The encoded protein has an EGF-like calcium binding domain and a seven transmembrane domain in the N-terminal region of the protein. Mutations in this gene are associated with congenital stationary night blindness type 1E. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-38326103-C-T is Benign according to our data. Variant chr17-38326103-C-T is described in ClinVar as [Benign]. Clinvar id is 322960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR179	NM_001004334.4	c.*362G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000616987.5	NP_001004334.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR179	ENST00000616987	c.*362G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_001004334.4	ENSP00000483469.2
GPR179	ENST00000622573.1	n.135-410G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 7193 AN: 152074 Hom.: 555 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.00815 AC: 634 AN: 77780 Hom.: 30 Cov.: 0 AF XY: 0.00749 AC XY: 295 AN XY: 39386

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.0153

Gnomad4 ASJ exome AF: 0.00382

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00179

Gnomad4 FIN exome AF: 0.000220

Gnomad4 NFE exome AF: 0.00153

Gnomad4 OTH exome AF: 0.0133

GnomAD4 genome AF: 0.0473 AC: 7206 AN: 152192 Hom.: 559 Cov.: 32 AF XY: 0.0452 AC XY: 3361 AN XY: 74412

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0205

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00137

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.00948 Hom.: 71

Bravo AF: 0.0539

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital stationary night blindness 1E Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4794777; hg19: chr17-36481986;