chr15-74181398-C-T

Position:

chr15-74181398-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000395105.9(STRA6):c.1581G>A(p.Met527Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,538 control chromosomes in the GnomAD database, including 15,095 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1292 hom., cov: 31)

Exomes 𝑓: 0.12 ( 13803 hom. )

Consequence

STRA6
ENST00000395105.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.382

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 -16 ACMG points.

BP6

Variant 15-74181398-C-T is Benign according to our data. Variant chr15-74181398-C-T is described in ClinVar as [Benign]. Clinvar id is 261578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRA6	NM_022369.4 linkuse as main transcript	c.1581G>A	p.Met527Ile	missense_variant	17/19	ENST00000395105.9	NP_071764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9 linkuse as main transcript	c.1581G>A	p.Met527Ile	missense_variant	17/19	1	NM_022369.4	ENSP00000378537	P1	Q9BX79-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17237

AN:

151742

Hom.:

1295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0865

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0870

Gnomad OTH

AF:

0.0971

GnomAD3 exomes

AF:

0.162

AC:

40521

AN:

250820

Hom.:

4592

AF XY:

0.162

AC XY:

22034

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.0840

Gnomad AMR exome

AF:

0.276

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.333

Gnomad SAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.0875

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.116

AC:

170199

AN:

1461678

Hom.:

13803

Cov.:

AF XY:

0.121

AC XY:

87983

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0788

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.340

Gnomad4 SAS exome

AF:

0.295

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.0893

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.113

AC:

17229

AN:

151860

Hom.:

1292

Cov.:

AF XY:

0.120

AC XY:

8902

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.0862

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.340

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0870

Gnomad4 OTH

AF:

0.0951

Alfa

AF:

0.100

Hom.:

1992

Bravo

AF:

0.114

TwinsUK

AF:

0.0860

AC:

319

ALSPAC

AF:

0.0838

AC:

323

ESP6500AA

AF:

0.0889

AC:

391

ESP6500EA

AF:

0.0860

AC:

739

ExAC

AF:

0.157

AC:

19101

Asia WGS

AF:

0.327

AC:

1135

AN:

3478

EpiCase

AF:

0.0899

EpiControl

AF:

0.0859

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Matthew-Wood syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
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:2

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.090

T;.;T;T;.;T;.;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.67

.;T;.;.;T;T;T;T;T

MetaRNN

Benign

0.0055

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;L;L;.;L;.;.;.

MutationTaster

Benign

0.87

P;P;P;P;P;P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

0.20

N;N;N;N;.;.;N;.;.

REVEL

Benign

0.15

Sift

Benign

0.85

T;T;T;T;.;.;T;.;.

Sift4G

Benign

0.23

T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;.;B;.;B;.

Vest4

0.049

MutPred

0.14

Gain of catalytic residue at M527 (P = 0.109);.;Gain of catalytic residue at M527 (P = 0.109);Gain of catalytic residue at M527 (P = 0.109);.;Gain of catalytic residue at M527 (P = 0.109);.;.;.;

MPC

0.10

ClinPred

0.011

GERP RS

3.8

Varity_R

0.044

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.62

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.62

Position offset: -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