15-74207639-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+1161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 1,468,988 control chromosomes in the GnomAD database, including 537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (281 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (256 hom.)
• Consequence: STRA6 ENST00000423167.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.432

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=-0.81).
• BP6: Variant 15-74207639-C-T is Benign according to our data. Variant chr15-74207639-C-T is described in ClinVar as [Benign]. Clinvar id is 1279498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_001142617.2	c.-16+1161G>A		intron_variant
STRA6	NM_001142619.2	c.-16+1161G>A		intron_variant
STRA6	NM_001142620.2	c.-16+1161G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000423167.6	c.-16+1161G>A		intron_variant		1
STRA6	ENST00000432245.6	c.-16+1161G>A		intron_variant		1
STRA6	ENST00000323940.9	c.-16+1161G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5245 AN: 152164 Hom.: 278 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.00379 AC: 4996 AN: 1316706 Hom.: 256 AF XY: 0.00330 AC XY: 2157 AN XY: 652858

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.00795

Gnomad4 ASJ exome AF: 0.000728

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000321

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000302

Gnomad4 OTH exome AF: 0.00866

GnomAD4 genome AF: 0.0346 AC: 5268 AN: 152282 Hom.: 281 Cov.: 32 AF XY: 0.0341 AC XY: 2541 AN XY: 74454

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0336 Hom.: 27

Bravo AF: 0.0394

Asia WGS AF: 0.00635 AC: 22 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

Oct 22, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.3
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7171215; hg19: chr15-74499980;