rs971757

Variant names:

• chr15-74195505-G-A
• rs971757
• ENST00000432245.6:c.*97C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142620.2(STRA6):​c.*97C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,607,720 control chromosomes in the GnomAD database, including 31,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2021 hom., cov: 31)
  • Exomes 𝑓: 0.19 (29244 hom.)
• Consequence: STRA6 NM_001142620.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.724
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• Matthew-Wood syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-74195505-G-A is Benign according to our data. Variant chr15-74195505-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294251.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142620.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	NM_022369.4	MANE Select	c.431-37C>T		intron	N/A	NP_071764.3
	STRA6	NM_001142620.2		c.*97C>T		3_prime_UTR	Exon 6 of 6	NP_001136092.1	Q9BX79-2
	STRA6	NM_001199042.2		c.548-37C>T		intron	N/A	NP_001185971.1	Q9BX79-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	ENST00000432245.6	TSL:1	c.*97C>T		3_prime_UTR	Exon 6 of 6	ENSP00000407176.2	Q9BX79-2
	STRA6	ENST00000395105.9	TSL:1 MANE Select	c.431-37C>T		intron	N/A	ENSP00000378537.4	Q9BX79-1
	STRA6	ENST00000563965.5	TSL:1	c.548-37C>T		intron	N/A	ENSP00000456609.1	Q9BX79-4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21022 AN: 151906 Hom.: 2021 Cov.: 31

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0322

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.144 AC: 34158 AN: 237372 AF XY: 0.144

Gnomad AFR exome AF: 0.0334

Gnomad AMR exome AF: 0.0650

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.000287

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.188 AC: 274329 AN: 1455696 Hom.: 29244 Cov.: 33 AF XY: 0.184 AC XY: 133307 AN XY: 723412

African (AFR) AF: 0.0277 AC: 928 AN: 33456

American (AMR) AF: 0.0661 AC: 2885 AN: 43626

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4788 AN: 25812

East Asian (EAS) AF: 0.000279 AC: 11 AN: 39464

South Asian (SAS) AF: 0.0472 AC: 3998 AN: 84692

European-Finnish (FIN) AF: 0.264 AC: 13972 AN: 52958

Middle Eastern (MID) AF: 0.0500 AC: 288 AN: 5756

European-Non Finnish (NFE) AF: 0.214 AC: 237311 AN: 1109718

Other (OTH) AF: 0.169 AC: 10148 AN: 60214

GnomAD4 genome AF: 0.138 AC: 21018 AN: 152024 Hom.: 2021 Cov.: 31 AF XY: 0.136 AC XY: 10115 AN XY: 74284

African (AFR) AF: 0.0367 AC: 1524 AN: 41500

American (AMR) AF: 0.0859 AC: 1312 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 650 AN: 3464

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5140

South Asian (SAS) AF: 0.0316 AC: 152 AN: 4816

European-Finnish (FIN) AF: 0.258 AC: 2719 AN: 10558

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14276 AN: 67950

Other (OTH) AF: 0.113 AC: 238 AN: 2112

Alfa AF: 0.175 Hom.: 552

Bravo AF: 0.121

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs971757; hg19: chr15-74487846; COSMIC: COSV60588017; COSMIC: COSV60588017;