15-74208006-C-G

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+794G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00364 in 1,393,930 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (90 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (56 hom.)
• Consequence: STRA6 ENST00000423167.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.155

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=-0.8).
• BP6: Variant 15-74208006-C-G is Benign according to our data. Variant chr15-74208006-C-G is described in ClinVar as [Benign]. Clinvar id is 1248750.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_001199041.2	c.-280G>C		5_prime_UTR_variant	1/19
STRA6	NM_001142617.2	c.-16+794G>C		intron_variant
STRA6	NM_001142619.2	c.-16+794G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000423167.6	c.-16+794G>C		intron_variant		1
STRA6	ENST00000432245.6	c.-16+794G>C		intron_variant		1
STRA6	ENST00000574278.5	c.-280G>C		5_prime_UTR_variant	1/19	2

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2772 AN: 152072 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00184 AC: 2285 AN: 1241740 Hom.: 56 Cov.: 31 AF XY: 0.00171 AC XY: 1022 AN XY: 598954

Gnomad4 AFR exome AF: 0.0642

Gnomad4 AMR exome AF: 0.00532

Gnomad4 ASJ exome AF: 0.000559

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000102

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000167

Gnomad4 OTH exome AF: 0.00419

GnomAD4 genome AF: 0.0183 AC: 2782 AN: 152190 Hom.: 90 Cov.: 32 AF XY: 0.0173 AC XY: 1291 AN XY: 74418

Gnomad4 AFR AF: 0.0637

Gnomad4 AMR AF: 0.00589

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0161 Hom.: 6

Bravo AF: 0.0207

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 21, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.6
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs74802269; hg19: chr15-74500347;