rs11857410

Variant names:

• chr15-74196083-G-A
• rs11857410
• NM_022369.4:c.331C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022369.4(STRA6):​c.331C>T​(p.Leu111Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,613,882 control chromosomes in the GnomAD database, including 31,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2096 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29442 hom.)
• Consequence: STRA6 NM_022369.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.19

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 15-74196083-G-A is Benign according to our data. Variant chr15-74196083-G-A is described in ClinVar as [Benign]. Clinvar id is 317117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRA6	NM_022369.4	c.331C>T	p.Leu111Leu	synonymous_variant	Exon 5 of 19	ENST00000395105.9	NP_071764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9	c.331C>T	p.Leu111Leu	synonymous_variant	Exon 5 of 19	1	NM_022369.4	ENSP00000378537.4

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22151 AN: 152026 Hom.: 2096 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.145 AC: 36275 AN: 250618 Hom.: 3577 AF XY: 0.144 AC XY: 19536 AN XY: 135574

Gnomad AFR exome AF: 0.0614

Gnomad AMR exome AF: 0.0655

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0455

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.189 AC: 276193 AN: 1461738 Hom.: 29442 Cov.: 33 AF XY: 0.185 AC XY: 134226 AN XY: 727152

Gnomad4 AFR exome AF: 0.0534

Gnomad4 AMR exome AF: 0.0669

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0472

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.146 AC: 22147 AN: 152144 Hom.: 2096 Cov.: 32 AF XY: 0.143 AC XY: 10654 AN XY: 74382

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.0877

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0317

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.118

Alfa AF: 0.186 Hom.: 5735

Bravo AF: 0.129

Asia WGS AF: 0.0270 AC: 92 AN: 3478

EpiCase AF: 0.186

EpiControl AF: 0.182

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Matthew-Wood syndrome Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.9
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11857410; hg19: chr15-74488424; COSMIC: COSV60584425; COSMIC: COSV60584425;