rs351224

Positions:

• chr15-74194695-T-A
• chr15-74194695-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000432245.6(STRA6):​c.*907A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,090,198 control chromosomes in the GnomAD database, including 116,914 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (16650 hom., cov: 32)
  • Exomes 𝑓: 0.46 (100264 hom.)
• Consequence: STRA6 ENST00000432245.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_022369.4	c.597+607A>T		intron_variant		ENST00000395105.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000395105.9	c.597+607A>T		intron_variant		1	NM_022369.4	P1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70277 AN: 151916 Hom.: 16630 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.460 AC: 431602 AN: 938164 Hom.: 100264 Cov.: 13 AF XY: 0.461 AC XY: 206510 AN XY: 447936

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.638

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.463 AC: 70337 AN: 152034 Hom.: 16650 Cov.: 32 AF XY: 0.467 AC XY: 34692 AN XY: 74312

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.519

Alfa AF: 0.448 Hom.: 1954

Bravo AF: 0.474

Asia WGS AF: 0.543 AC: 1893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs351224; hg19: chr15-74487036;