15-74209236-G-A

Position:

• chr15-74209236-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001199040.2(STRA6):​c.96+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,135,544 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (6 hom.)
• Consequence: STRA6 NM_001199040.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.838

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 15-74209236-G-A is Benign according to our data. Variant chr15-74209236-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1707199.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00718 (1093/152256) while in subpopulation AFR AF= 0.0249 (1035/41544). AF 95% confidence interval is 0.0237. There are 12 homozygotes in gnomad4. There are 517 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRA6	NM_001199040.2	c.96+123C>T		intron_variant			NP_001185969.1
CCDC33	XM_047433141.1	c.-416-152G>A		intron_variant			XP_047289097.1
STRA6	XM_011521883.1	c.-16+2891C>T		intron_variant			XP_011520185.1
STRA6	XM_017022479.2	c.-48+2891C>T		intron_variant			XP_016877968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000535552.5	c.96+123C>T		intron_variant		2		ENSP00000440238.1
STRA6	ENST00000449139.6	c.-16+2891C>T		intron_variant		5		ENSP00000410221.2
STRA6	ENST00000416286.7	c.-16+2891C>T		intron_variant		5		ENSP00000400403.3

Frequencies

GnomAD3 genomes AF: 0.00719 AC: 1094 AN: 152138 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00671

GnomAD4 exome AF: 0.000783 AC: 770 AN: 983288 Hom.: 6 AF XY: 0.000648 AC XY: 323 AN XY: 498378

Gnomad4 AFR exome AF: 0.0242

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000237

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000664

Gnomad4 OTH exome AF: 0.00189

GnomAD4 genome AF: 0.00718 AC: 1093 AN: 152256 Hom.: 12 Cov.: 32 AF XY: 0.00694 AC XY: 517 AN XY: 74450

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00344 Hom.: 1

Bravo AF: 0.00800

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 09, 2018

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	19
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7179079; hg19: chr15-74501577;