15-74179858-C-T

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.*222G>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 0.64 in 588,096 control chromosomes in the GnomAD database, including 125,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (27222 hom., cov: 32)
  • Exomes 𝑓: 0.66 (97911 hom.)
• Consequence: STRA6 NM_022369.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.213

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=-0.83).
• BP6: Variant 15-74179858-C-T is Benign according to our data. Variant chr15-74179858-C-T is described in ClinVar as [Benign]. Clinvar id is 317085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_022369.4	c.*222G>A		3_prime_UTR_variant	19/19	ENST00000395105.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000395105.9	c.*222G>A		3_prime_UTR_variant	19/19	1	NM_022369.4	P1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86710 AN: 152034 Hom.: 27206 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.664 AC: 289333 AN: 435944 Hom.: 97911 Cov.: 5 AF XY: 0.666 AC XY: 150567 AN XY: 225932

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.657

Gnomad4 ASJ exome AF: 0.665

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.645

GnomAD4 genome AF: 0.570 AC: 86767 AN: 152152 Hom.: 27222 Cov.: 32 AF XY: 0.571 AC XY: 42494 AN XY: 74378

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.662

Alfa AF: 0.686 Hom.: 40632

Bravo AF: 0.565

Asia WGS AF: 0.577 AC: 2010 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

Jun 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.2
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs10910; hg19: chr15-74472199; COSMIC: COSV51433327; COSMIC: COSV51433327;