15-74194103-C-T

Position:

• chr15-74194103-C-T

Variant summary

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

The NM_022369.4(STRA6):​c.598-181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,906 control chromosomes in the GnomAD database, including 10,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.35 (10388 hom., cov: 31)
• Consequence: STRA6 NM_022369.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.00

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]

STRA6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-74194103-C-T is Benign according to our data. Variant chr15-74194103-C-T is described in ClinVar as [Benign]. Clinvar id is 1285943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRA6	NM_022369.4	c.598-181G>A		intron_variant		ENST00000395105.9	NP_071764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9	c.598-181G>A		intron_variant		1	NM_022369.4	ENSP00000378537.4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52986 AN: 151788 Hom.: 10356 Cov.: 31

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.349 AC: 53063 AN: 151906 Hom.: 10388 Cov.: 31 AF XY: 0.350 AC XY: 25985 AN XY: 74252

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.289

Alfa AF: 0.256 Hom.: 4921

Bravo AF: 0.354

Asia WGS AF: 0.339 AC: 1179 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	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs974456; hg19: chr15-74486444;