rs201408425

Positions:

chr15-74182370-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022369.4(STRA6):c.1391T>G(p.Leu464Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000153 in 1,614,028 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 3 hom. )

Consequence

STRA6
NM_022369.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.13

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=0.06258991).

BP6

Variant 15-74182370-A-C is Benign according to our data. Variant chr15-74182370-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 464031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000217 (33/152304) while in subpopulation AMR AF= 0.00183 (28/15306). AF 95% confidence interval is 0.0013. There are 1 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_022369.4 linkuse as main transcript	c.1391T>G	p.Leu464Arg	missense_variant	15/19	ENST00000395105.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000395105.9 linkuse as main transcript	c.1391T>G	p.Leu464Arg	missense_variant	15/19	1	NM_022369.4	P1	Q9BX79-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000590

AC:

148

AN:

250932

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00417

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000146

AC:

214

AN:

1461724

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00432

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000217

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000674

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000404

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Matthew-Wood syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

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

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.95

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.063

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

MetaSVM

Uncertain

0.14

MutationAssessor

Uncertain

2.7

M;.;M;M;.;M;.;.;.

MutationTaster

Benign

0.63

D;D;D;N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.0

D;D;D;.;.;.;D;.;.

REVEL

Pathogenic

0.71

Sift

Uncertain

0.011

D;D;D;.;.;.;D;.;.

Sift4G

Uncertain

0.0050

D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;.;D;.;D;.

Vest4

0.68

MVP

0.87

MPC

0.55

ClinPred

0.067

GERP RS

4.8

Varity_R

0.32

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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