15-74207615-G-C

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+1185C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,332,430 control chromosomes in the GnomAD database, including 106,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12492 hom., cov: 32)
  • Exomes 𝑓: 0.39 (93867 hom.)
• Consequence: STRA6 ENST00000423167.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.355

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=-0.84).
• BP6: Variant 15-74207615-G-C is Benign according to our data. Variant chr15-74207615-G-C is described in ClinVar as [Benign]. Clinvar id is 1225093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_001142617.2	c.-16+1185C>G		intron_variant
STRA6	NM_001142619.2	c.-16+1185C>G		intron_variant
STRA6	NM_001142620.2	c.-16+1185C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000423167.6	c.-16+1185C>G		intron_variant		1
STRA6	ENST00000432245.6	c.-16+1185C>G		intron_variant		1
STRA6	ENST00000323940.9	c.-16+1185C>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60360 AN: 151918 Hom.: 12475 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.391 AC: 460975 AN: 1180394 Hom.: 93867 AF XY: 0.396 AC XY: 233363 AN XY: 589644

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.538

Gnomad4 SAS exome AF: 0.588

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.397 AC: 60420 AN: 152036 Hom.: 12492 Cov.: 32 AF XY: 0.406 AC XY: 30176 AN XY: 74320

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.426

Alfa AF: 0.210 Hom.: 445

Bravo AF: 0.407

Asia WGS AF: 0.546 AC: 1902 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

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.6
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs351222; hg19: chr15-74499956;