rs11857410

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.19

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

Matthew-Wood syndrome
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet
microphthalmia, isolated, with coloboma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

STRA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 link	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 link	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.:

show subpopulations

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

GnomAD2 exomes

AF:

0.145

AC:

36275

AN:

250618

AF XY:

0.144

show subpopulations

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 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.:

AF XY:

0.185

AC XY:

134226

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.0534

AC:

1787

AN:

33478

American (AMR)

AF:

0.0669

AC:

2993

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

4841

AN:

26134

East Asian (EAS)

AF:

0.000277

AC:

AN:

39700

South Asian (SAS)

AF:

0.0472

AC:

4074

AN:

86252

European-Finnish (FIN)

AF:

0.264

AC:

14066

AN:

53334

Middle Eastern (MID)

AF:

0.0512

AC:

295

AN:

5766

European-Non Finnish (NFE)

AF:

0.214

AC:

237850

AN:

1111968

Other (OTH)

AF:

0.170

AC:

10276

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14153

28306

42459

56612

70765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7994

15988

23982

31976

39970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.146

AC:

22147

AN:

152144

Hom.:

2096

Cov.:

AF XY:

0.143

AC XY:

10654

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0622

AC:

2583

AN:

41520

American (AMR)

AF:

0.0877

AC:

1341

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

650

AN:

3468

East Asian (EAS)

AF:

0.00135

AC:

AN:

5182

South Asian (SAS)

AF:

0.0317

AC:

153

AN:

4822

European-Finnish (FIN)

AF:

0.258

AC:

2733

AN:

10590

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14289

AN:

67952

Other (OTH)

AF:

0.118

AC:

250

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

921

1842

2763

3684

4605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.177

Hom.:

8883

Bravo

AF:

0.129

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.186

EpiControl

AF:

0.182

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Matthew-Wood syndrome

Benign:2

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.

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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_noAF

Benign

-0.66

CADD

Benign

8.9

(source)

DANN

Benign

0.74

PhyloP100

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over