rs351224

Variant names:

• chr15-74194695-T-A
• rs351224
• ENST00000432245.6:c.*907A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-74194695-T-A
• chr15-74194695-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142620.2(STRA6):​c.*907A>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 0.46 in 1,090,198 control chromosomes in the GnomAD database, including 116,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.46 (16650 hom., cov: 32)
  • Exomes 𝑓: 0.46 (100264 hom.)
• Consequence: STRA6 NM_001142620.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.592 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.597+607A>T		intron	N/A	NP_071764.3
	STRA6	NM_001142620.2		c.*907A>T		3_prime_UTR	Exon 6 of 6	NP_001136092.1	Q9BX79-2
	STRA6	NM_001199042.2		c.714+607A>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.*907A>T		3_prime_UTR	Exon 6 of 6	ENSP00000407176.2	Q9BX79-2
	STRA6	ENST00000395105.9	TSL:1 MANE Select	c.597+607A>T		intron	N/A	ENSP00000378537.4	Q9BX79-1
	STRA6	ENST00000563965.5	TSL:1	c.714+607A>T		intron	N/A	ENSP00000456609.1	Q9BX79-4

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70277 AN: 151916 Hom.: 16630 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.460 AC: 431602 AN: 938164 Hom.: 100264 Cov.: 13 AF XY: 0.461 AC XY: 206510 AN XY: 447936

African (AFR) AF: 0.416 AC: 8333 AN: 20026

American (AMR) AF: 0.638 AC: 7082 AN: 11094

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 7160 AN: 13620

East Asian (EAS) AF: 0.547 AC: 14602 AN: 26698

South Asian (SAS) AF: 0.579 AC: 10058 AN: 17364

European-Finnish (FIN) AF: 0.414 AC: 8830 AN: 21346

Middle Eastern (MID) AF: 0.536 AC: 1413 AN: 2634

European-Non Finnish (NFE) AF: 0.452 AC: 355125 AN: 785944

Other (OTH) AF: 0.482 AC: 18999 AN: 39438

GnomAD4 genome AF: 0.463 AC: 70337 AN: 152034 Hom.: 16650 Cov.: 32 AF XY: 0.467 AC XY: 34692 AN XY: 74312

African (AFR) AF: 0.416 AC: 17248 AN: 41456

American (AMR) AF: 0.603 AC: 9205 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2640 AN: 5178

South Asian (SAS) AF: 0.590 AC: 2836 AN: 4806

European-Finnish (FIN) AF: 0.411 AC: 4343 AN: 10576

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30550 AN: 67956

Other (OTH) AF: 0.519 AC: 1098 AN: 2114

Alfa AF: 0.448 Hom.: 1954

Bravo AF: 0.474

Asia WGS AF: 0.543 AC: 1893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
DANN	Benign	0.86
PhyloP100		0.26
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: rs351224; hg19: chr15-74487036;