rs12913041

Variant names:

• chr15-74180961-A-G
• rs12913041
• NM_022369.4:c.1685-24T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022369.4(STRA6):​c.1685-24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,612,240 control chromosomes in the GnomAD database, including 32,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2273 hom., cov: 31)
  • Exomes 𝑓: 0.19 (30377 hom.)
• Consequence: STRA6 NM_022369.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0960
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-74180961-A-G is Benign according to our data. Variant chr15-74180961-A-G is described in ClinVar as [Benign]. Clinvar id is 1239030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRA6	NM_022369.4	c.1685-24T>C		intron_variant	Intron 17 of 18	ENST00000395105.9	NP_071764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9	c.1685-24T>C		intron_variant	Intron 17 of 18	1	NM_022369.4	ENSP00000378537.4

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22970 AN: 151844 Hom.: 2270 Cov.: 31

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.150 AC: 37314 AN: 249202 AF XY: 0.149

Gnomad AFR exome AF: 0.0656

Gnomad AMR exome AF: 0.0684

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.275

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.192 AC: 280579 AN: 1460278 Hom.: 30377 Cov.: 34 AF XY: 0.188 AC XY: 136425 AN XY: 726264

African (AFR) AF: 0.0619 AC: 2073 AN: 33466

American (AMR) AF: 0.0684 AC: 3057 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5392 AN: 26090

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39682

South Asian (SAS) AF: 0.0489 AC: 4218 AN: 86188

European-Finnish (FIN) AF: 0.283 AC: 14870 AN: 52618

Middle Eastern (MID) AF: 0.0543 AC: 313 AN: 5764

European-Non Finnish (NFE) AF: 0.216 AC: 239992 AN: 1111424

Other (OTH) AF: 0.177 AC: 10654 AN: 60350

GnomAD4 genome AF: 0.151 AC: 22979 AN: 151962 Hom.: 2273 Cov.: 31 AF XY: 0.150 AC XY: 11109 AN XY: 74300

African (AFR) AF: 0.0677 AC: 2807 AN: 41454

American (AMR) AF: 0.0926 AC: 1416 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3468

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5154

South Asian (SAS) AF: 0.0324 AC: 156 AN: 4814

European-Finnish (FIN) AF: 0.275 AC: 2907 AN: 10580

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14555 AN: 67890

Other (OTH) AF: 0.126 AC: 265 AN: 2108

Alfa AF: 0.186 Hom.: 600

Bravo AF: 0.134

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.29
PhyloP100		0.096
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12913041; hg19: chr15-74473302; COSMIC: COSV51435057; COSMIC: COSV51435057;