15-74207712-C-T

Variant summary

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

The ENST00000423167.6(STRA6):c.-16+1088G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,535,694 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (54 hom.)
• Consequence: STRA6 ENST00000423167.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.602

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]

CCDC33 (HGNC:26552): (coiled-coil domain containing 33) Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-74207712-C-T is Benign according to our data. Variant chr15-74207712-C-T is described in ClinVar as [Benign]. Clinvar id is 1248987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_001199041.2	c.15G>A	p.Gly5=	synonymous_variant	1/19
STRA6	NM_001142617.2	c.-16+1088G>A		intron_variant
STRA6	NM_001142619.2	c.-16+1088G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000423167.6	c.-16+1088G>A		intron_variant		1
STRA6	ENST00000432245.6	c.-16+1088G>A		intron_variant		1
STRA6	ENST00000574278.5	c.15G>A	p.Gly5=	synonymous_variant	1/19	2

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 391 AN: 152178 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00508 AC: 652 AN: 128470 Hom.: 20 AF XY: 0.00489 AC XY: 344 AN XY: 70350

Gnomad AFR exome AF: 0.000163

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0585

Gnomad SAS exome AF: 0.000893

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000419

Gnomad OTH exome AF: 0.00450

GnomAD4 exome AF: 0.00159 AC: 2195 AN: 1383398 Hom.: 54 Cov.: 30 AF XY: 0.00159 AC XY: 1085 AN XY: 682598

Gnomad4 AFR exome AF: 0.0000633

Gnomad4 AMR exome AF: 0.0000560

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0501

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.0000299

Gnomad4 NFE exome AF: 0.0000250

Gnomad4 OTH exome AF: 0.00487

GnomAD4 genome AF: 0.00255 AC: 389 AN: 152296 Hom.: 16 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74468

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0698

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000538 Hom.: 1

Bravo AF: 0.00259

Asia WGS AF: 0.0350 AC: 120 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

May 21, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.74
Dann	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76528848; hg19: chr15-74500053; COSMIC: COSV100120846; COSMIC: COSV100120846;