15-74207739-G-C

Position:

• chr15-74207739-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001199041.2(STRA6):​c.-13C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,535,722 control chromosomes in the GnomAD database, including 577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (39 hom., cov: 32)
  • Exomes 𝑓: 0.025 (538 hom.)
• Consequence: STRA6 NM_001199041.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.724

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]

CCDC33 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-74207739-G-C is Benign according to our data. Variant chr15-74207739-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1204061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0222 (3380/152320) while in subpopulation EAS AF= 0.0403 (209/5184). AF 95% confidence interval is 0.0358. There are 39 homozygotes in gnomad4. There are 1599 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRA6	NM_001199041.2	c.-13C>G		5_prime_UTR_premature_start_codon_gain_variant	1/19		NP_001185970.1
STRA6	NM_001199041.2	c.-13C>G		5_prime_UTR_variant	1/19		NP_001185970.1
STRA6	NM_001199040.2	c.96+1620C>G		intron_variant			NP_001185969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000423167.6	c.-16+1061C>G		intron_variant		1		ENSP00000413012.2
STRA6	ENST00000432245.6	c.-16+1061C>G		intron_variant		1		ENSP00000407176.2
STRA6	ENST00000574278.5	c.-13C>G		5_prime_UTR_premature_start_codon_gain_variant	1/19	2		ENSP00000458827.1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3376 AN: 152202 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0405

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0251 AC: 3224 AN: 128472 Hom.: 68 AF XY: 0.0270 AC XY: 1900 AN XY: 70352

Gnomad AFR exome AF: 0.0181

Gnomad AMR exome AF: 0.00756

Gnomad ASJ exome AF: 0.0276

Gnomad EAS exome AF: 0.0420

Gnomad SAS exome AF: 0.0406

Gnomad FIN exome AF: 0.0212

Gnomad NFE exome AF: 0.0242

Gnomad OTH exome AF: 0.0235

GnomAD4 exome AF: 0.0254 AC: 35109 AN: 1383402 Hom.: 538 Cov.: 31 AF XY: 0.0258 AC XY: 17635 AN XY: 682602

Gnomad4 AFR exome AF: 0.0187

Gnomad4 AMR exome AF: 0.00798

Gnomad4 ASJ exome AF: 0.0289

Gnomad4 EAS exome AF: 0.0324

Gnomad4 SAS exome AF: 0.0412

Gnomad4 FIN exome AF: 0.0216

Gnomad4 NFE exome AF: 0.0247

Gnomad4 OTH exome AF: 0.0274

GnomAD4 genome AF: 0.0222 AC: 3380 AN: 152320 Hom.: 39 Cov.: 32 AF XY: 0.0215 AC XY: 1599 AN XY: 74492

Gnomad4 AFR AF: 0.0195

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0402

Gnomad4 FIN AF: 0.0200

Gnomad4 NFE AF: 0.0239

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.0154 Hom.: 8

Bravo AF: 0.0210

Asia WGS AF: 0.0500 AC: 172 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.074
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77704192; hg19: chr15-74500080;