rs34147822

Positions:

• chr15-74195911-T-C

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.406+97A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,543,162 control chromosomes in the GnomAD database, including 30,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2040 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28034 hom.)
• Consequence: STRA6 NM_022369.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.265

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=-0.82).
• BP6: Variant 15-74195911-T-C is Benign according to our data. Variant chr15-74195911-T-C is described in ClinVar as [Benign]. Clinvar id is 1288646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRA6	NM_022369.4	c.406+97A>G		intron_variant		ENST00000395105.9	NP_071764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9	c.406+97A>G		intron_variant		1	NM_022369.4	ENSP00000378537.4

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21371 AN: 152066 Hom.: 2040 Cov.: 32

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0861

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.189 AC: 262792 AN: 1390978 Hom.: 28034 AF XY: 0.185 AC XY: 127616 AN XY: 690542

Gnomad4 AFR exome AF: 0.0361

Gnomad4 AMR exome AF: 0.0667

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.000237

Gnomad4 SAS exome AF: 0.0469

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.140 AC: 21369 AN: 152184 Hom.: 2040 Cov.: 32 AF XY: 0.138 AC XY: 10286 AN XY: 74400

Gnomad4 AFR AF: 0.0444

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0320

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.113

Alfa AF: 0.186 Hom.: 392

Bravo AF: 0.124

Asia WGS AF: 0.0250 AC: 86 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	Apr 16, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.60

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: rs34147822; hg19: chr15-74488252;