15-74179953-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022369.4(STRA6):c.*127T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,301,488 control chromosomes in the GnomAD database, including 26,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2320 hom., cov: 33)
  • Exomes 𝑓: 0.19 (24180 hom.)
• Consequence: STRA6 NM_022369.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.30

Genes affected

STRA6 (HGNC:30650): (signaling receptor and transporter of retinol STRA6) The protein encoded by this gene is a membrane protein involved in the metabolism of retinol. The encoded protein acts as a receptor for retinol/retinol binding protein complexes. This protein removes the retinol from the complex and transports it across the cell membrane. Defects in this gene are a cause of syndromic microphthalmia type 9 (MCOPS9). Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-74179953-A-G is Benign according to our data. Variant chr15-74179953-A-G is described in ClinVar as [Benign]. Clinvar id is 317089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_022369.4	c.*127T>C		3_prime_UTR_variant	19/19	ENST00000395105.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000395105.9	c.*127T>C		3_prime_UTR_variant	19/19	1	NM_022369.4	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23812 AN: 152106 Hom.: 2316 Cov.: 33

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.192 AC: 220690 AN: 1149264 Hom.: 24180 Cov.: 16 AF XY: 0.187 AC XY: 107162 AN XY: 572182

Gnomad4 AFR exome AF: 0.0873

Gnomad4 AMR exome AF: 0.0654

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.000266

Gnomad4 SAS exome AF: 0.0466

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.157 AC: 23824 AN: 152224 Hom.: 2320 Cov.: 33 AF XY: 0.155 AC XY: 11544 AN XY: 74422

Gnomad4 AFR AF: 0.0909

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0302

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.123

Alfa AF: 0.180 Hom.: 2485

Bravo AF: 0.139

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Matthew-Wood syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.11
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11631944; hg19: chr15-74472294;