rs115067613

Variant names:

• chr15-74196047-C-G
• rs115067613
• NM_022369.4:c.367G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-74196047-C-G
• chr15-74196047-C-A
• chr15-74196047-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_022369.4(STRA6):​c.367G>C​(p.Ala123Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,613,966 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (20 hom.)
• Consequence: STRA6 NM_022369.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.08
• Publications: 1 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 (MetaRNN=0.0035663843).
• BP6: Variant 15-74196047-C-G is Benign according to our data. Variant chr15-74196047-C-G is described in ClinVar as Benign. ClinVar VariationId is 464034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00731 (1112/152204) while in subpopulation AFR AF = 0.0257 (1066/41516). AF 95% confidence interval is 0.0244. There are 16 homozygotes in GnomAd4. There are 532 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022369.4. 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.367G>C	p.Ala123Pro	missense	Exon 5 of 19	NP_071764.3
	STRA6	NM_001199042.2		c.484G>C	p.Ala162Pro	missense	Exon 5 of 19	NP_001185971.1	Q9BX79-4
	STRA6	NM_001199040.2		c.478G>C	p.Ala160Pro	missense	Exon 5 of 19	NP_001185969.1	Q9BX79-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	ENST00000395105.9	TSL:1 MANE Select	c.367G>C	p.Ala123Pro	missense	Exon 5 of 19	ENSP00000378537.4	Q9BX79-1
	STRA6	ENST00000563965.5	TSL:1	c.484G>C	p.Ala162Pro	missense	Exon 5 of 19	ENSP00000456609.1	Q9BX79-4
	STRA6	ENST00000423167.6	TSL:1	c.340G>C	p.Ala114Pro	missense	Exon 5 of 19	ENSP00000413012.2	Q9BX79-3

Frequencies

GnomAD3 genomes AF: 0.00732 AC: 1114 AN: 152086 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00205 AC: 513 AN: 250656 AF XY: 0.00142

Gnomad AFR exome AF: 0.0285

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000711 AC: 1039 AN: 1461762 Hom.: 20 Cov.: 31 AF XY: 0.000582 AC XY: 423 AN XY: 727162

African (AFR) AF: 0.0259 AC: 866 AN: 33480

American (AMR) AF: 0.00119 AC: 53 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5762

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111990

Other (OTH) AF: 0.00159 AC: 96 AN: 60388

GnomAD4 genome AF: 0.00731 AC: 1112 AN: 152204 Hom.: 16 Cov.: 32 AF XY: 0.00715 AC XY: 532 AN XY: 74428

African (AFR) AF: 0.0257 AC: 1066 AN: 41516

American (AMR) AF: 0.00203 AC: 31 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00664 AC: 14 AN: 2110

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.00836

ESP6500AA AF: 0.0259 AC: 114

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00228 AC: 277

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Matthew-Wood syndrome (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.63
DEOGEN2	Benign	0.073	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.1	N
PhyloP100		2.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	3.1	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.093
MVP		0.61
MPC		0.12
ClinPred		0.0066	T
GERP RS		4.3
Varity_R		0.088
gMVP		0.54
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs115067613; hg19: chr15-74488388;