Genetic Variant STRA6:p.Leu152Met (chr15-74195628-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142620.2(STRA6):c.454T>A(p.Leu152Met) variant causes a missense 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. 12/14 in silico tools predict 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
NM_001142620.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.425

Variant links:

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]

STRA6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
STRA6	NM_022369.4 link	c.430+24T>A		intron_variant	Intron 6 of 18	ENST00000395105.9	NP_071764.3	Q9BX79-1B3KPB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9 link	c.430+24T>A		intron_variant	Intron 6 of 18	1	NM_022369.4	ENSP00000378537.4		Q9BX79-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21038

AN:

151704

Hom.:

2026

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.185

AC XY:

127364

AN XY:

686706

show subpopulations

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.:

AF XY:

0.137

AC XY:

10125

AN XY:

74172

show subpopulations

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:

ESP6500EA

AF:

0.218

AC:

1006

ExAC

AF:

0.0814

AC:

5474

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

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

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.64

REVEL

Benign

0.23

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.90

Vest4

0.14

ClinPred

0.0074

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over