rs35255788

chr15-74195897-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022369.4(STRA6):c.406+111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,475,066 control chromosomes in the GnomAD database, including 28,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2089 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26852 hom.)
• Consequence: STRA6 NM_022369.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.46

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-74195897-T-C is Benign according to our data. Variant chr15-74195897-T-C is described in ClinVar as [Benign]. Clinvar id is 1290883.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
STRA6	NM_022369.4	c.406+111A>G		intron_variant		ENST00000395105.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000395105.9	c.406+111A>G		intron_variant		1	NM_022369.4	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22139 AN: 151978 Hom.: 2089 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.190 AC: 251270 AN: 1322970 Hom.: 26852 AF XY: 0.186 AC XY: 121906 AN XY: 656884

Gnomad4 AFR exome AF: 0.0537

Gnomad4 AMR exome AF: 0.0678

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.000245

Gnomad4 SAS exome AF: 0.0469

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.146 AC: 22133 AN: 152096 Hom.: 2089 Cov.: 32 AF XY: 0.143 AC XY: 10644 AN XY: 74350

Gnomad4 AFR AF: 0.0621

Gnomad4 AMR AF: 0.0879

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0320

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.118

Alfa AF: 0.173 Hom.: 403

Bravo AF: 0.129

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.62
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs35255788; hg19: chr15-74488238;