15-74203033-A-C

Position:

• chr15-74203033-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142618.2(STRA6):​c.-46T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 985,752 control chromosomes in the GnomAD database, including 20,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2035 hom., cov: 32)
  • Exomes 𝑓: 0.21 (18819 hom.)
• Consequence: STRA6 NM_001142618.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.476

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=-0.85).
• BP6: Variant 15-74203033-A-C is Benign according to our data. Variant chr15-74203033-A-C is described in ClinVar as [Benign]. Clinvar id is 1260403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRA6	NM_001142618.2	c.-46T>G		5_prime_UTR_variant	1/19		NP_001136090.1
CCDC33	XM_047433141.1	c.-482A>C		5_prime_UTR_variant	1/23		XP_047289097.1
STRA6	NM_001199040.2	c.97-751T>G		intron_variant			NP_001185969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000423167.6	c.-15-751T>G		intron_variant		1		ENSP00000413012.2
STRA6	ENST00000432245.6	c.-15-751T>G		intron_variant		1		ENSP00000407176.2
STRA6	ENST00000569936.5	n.-46T>G		non_coding_transcript_exon_variant	1/14	1		ENSP00000461799.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21366 AN: 152036 Hom.: 2035 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.208 AC: 173273 AN: 833598 Hom.: 18819 Cov.: 34 AF XY: 0.208 AC XY: 79995 AN XY: 385058

Gnomad4 AFR exome AF: 0.0255

Gnomad4 AMR exome AF: 0.0630

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.00138

Gnomad4 SAS exome AF: 0.0488

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.140 AC: 21360 AN: 152154 Hom.: 2035 Cov.: 32 AF XY: 0.139 AC XY: 10303 AN XY: 74384

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.0873

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.112

Alfa AF: 0.110 Hom.: 233

Bravo AF: 0.123

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62003660; hg19: chr15-74495374;