15-74208389-C-T

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+411G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 152,210 control chromosomes in the GnomAD database, including 72,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.97 (72413 hom., cov: 31)
• Consequence: STRA6 ENST00000423167.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67

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=-0.85).
• BP6: Variant 15-74208389-C-T is Benign according to our data. Variant chr15-74208389-C-T is described in ClinVar as [Benign]. Clinvar id is 1286131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_001142617.2	c.-16+411G>A		intron_variant
STRA6	NM_001142619.2	c.-16+411G>A		intron_variant
STRA6	NM_001142620.2	c.-16+411G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000423167.6	c.-16+411G>A		intron_variant		1
STRA6	ENST00000432245.6	c.-16+411G>A		intron_variant		1
STRA6	ENST00000323940.9	c.-16+411G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.975 AC: 148258 AN: 152092 Hom.: 72359 Cov.: 31

Gnomad AFR AF: 0.912

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.981

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.975 AC: 148369 AN: 152210 Hom.: 72413 Cov.: 31 AF XY: 0.976 AC XY: 72604 AN XY: 74420

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.992

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.981

Alfa AF: 0.991 Hom.: 4042

Bravo AF: 0.972

Asia WGS AF: 0.994 AC: 3456 AN: 3478

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

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.22
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs351221; hg19: chr15-74500730;