15-74207897-C-T

Position:

• chr15-74207897-C-T

Variant summary

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

The NM_001199041.2(STRA6):​c.-171G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,489,078 control chromosomes in the GnomAD database, including 45,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4016 hom., cov: 32)
  • Exomes 𝑓: 0.25 (41862 hom.)
• Consequence: STRA6 NM_001199041.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.55

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=-0.84).
• BP6: Variant 15-74207897-C-T is Benign according to our data. Variant chr15-74207897-C-T is described in ClinVar as [Benign]. Clinvar id is 675104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRA6	NM_001199041.2	c.-171G>A		5_prime_UTR_variant	1/19		NP_001185970.1
STRA6	NM_001199040.2	c.96+1462G>A		intron_variant			NP_001185969.1
STRA6	NM_001142617.2	c.-16+903G>A		intron_variant			NP_001136089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000423167.6	c.-16+903G>A		intron_variant		1		ENSP00000413012.2
STRA6	ENST00000432245.6	c.-16+903G>A		intron_variant		1		ENSP00000407176.2
STRA6	ENST00000574278.5	c.-171G>A		5_prime_UTR_variant	1/19	2		ENSP00000458827.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33919 AN: 151934 Hom.: 4019 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.248 AC: 331136 AN: 1337026 Hom.: 41862 Cov.: 31 AF XY: 0.247 AC XY: 161220 AN XY: 652920

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.223 AC: 33922 AN: 152052 Hom.: 4016 Cov.: 32 AF XY: 0.222 AC XY: 16513 AN XY: 74320

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.233

Alfa AF: 0.234 Hom.: 543

Bravo AF: 0.220

Asia WGS AF: 0.237 AC: 825 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	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.061
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10152959; hg19: chr15-74500238;