rs971756

Positions:

• chr15-74195628-A-T

Variant summary

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

The ENST00000395105.9(STRA6):​c.430+24T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,543,242 control chromosomes in the GnomAD database, including 30,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2026 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28245 hom.)
• Consequence: STRA6 ENST00000395105.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.425

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 (MetaRNN=0.003751129).
• BP6: Variant 15-74195628-A-T is Benign according to our data. Variant chr15-74195628-A-T is described in ClinVar as [Benign]. Clinvar id is 1183162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRA6	NM_022369.4	c.430+24T>A		intron_variant		ENST00000395105.9	NP_071764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9	c.430+24T>A		intron_variant		1	NM_022369.4	ENSP00000378537	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21038 AN: 151704 Hom.: 2026 Cov.: 32

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0862

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.138 AC: 21697 AN: 156878 Hom.: 2111 AF XY: 0.136 AC XY: 11240 AN XY: 82544

Gnomad AFR exome AF: 0.0323

Gnomad AMR exome AF: 0.0684

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.000351

Gnomad SAS exome AF: 0.0472

Gnomad FIN exome AF: 0.257

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.190 AC: 263920 AN: 1391420 Hom.: 28245 Cov.: 29 AF XY: 0.185 AC XY: 127364 AN XY: 686706

Gnomad4 AFR exome AF: 0.0276

Gnomad4 AMR exome AF: 0.0692

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.000280

Gnomad4 SAS exome AF: 0.0476

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.139 AC: 21034 AN: 151822 Hom.: 2026 Cov.: 32 AF XY: 0.137 AC XY: 10125 AN XY: 74172

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0321

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.112

Alfa AF: 0.193 Hom.: 2356

Bravo AF: 0.121

TwinsUK AF: 0.222 AC: 823

ALSPAC AF: 0.213 AC: 820

ESP6500AA AF: 0.0374 AC: 99

ESP6500EA AF: 0.218 AC: 1006

ExAC AF: 0.0814 AC: 5474

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.5
DANN	Benign	0.94
Eigen	Benign	-0.81
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.90	P
Vest4		0.14
ClinPred		0.0074	T
GERP RS		-2.4

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: rs971756; hg19: chr15-74487969;