rs12912578

Variant names:

• chr15-74180732-A-G
• rs12912578
• NM_022369.4:c.1840+50T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-74180732-A-G
• chr15-74180732-A-C

Variant summary

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

The NM_022369.4(STRA6):​c.1840+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,563,154 control chromosomes in the GnomAD database, including 31,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2276 hom., cov: 31)
  • Exomes 𝑓: 0.19 (29627 hom.)
• Consequence: STRA6 NM_022369.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.329
• Publications: 7 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=-0.9).
• BP6: Variant 15-74180732-A-G is Benign according to our data. Variant chr15-74180732-A-G is described in ClinVar as Benign. ClinVar VariationId is 1265464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

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.1840+50T>C		intron	N/A	NP_071764.3
	STRA6	NM_001199042.2		c.1957+50T>C		intron	N/A	NP_001185971.1	Q9BX79-4
	STRA6	NM_001199040.2		c.1951+50T>C		intron	N/A	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.1840+50T>C		intron	N/A	ENSP00000378537.4	Q9BX79-1
	STRA6	ENST00000563965.5	TSL:1	c.1957+50T>C		intron	N/A	ENSP00000456609.1	Q9BX79-4
	STRA6	ENST00000423167.6	TSL:1	c.1813+50T>C		intron	N/A	ENSP00000413012.2	Q9BX79-3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22938 AN: 151922 Hom.: 2273 Cov.: 31

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0937

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.129

GnomAD2 exomes AF: 0.151 AC: 33850 AN: 223636 AF XY: 0.151

Gnomad AFR exome AF: 0.0637

Gnomad AMR exome AF: 0.0703

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.000280

Gnomad FIN exome AF: 0.276

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.193 AC: 272822 AN: 1411112 Hom.: 29627 Cov.: 32 AF XY: 0.189 AC XY: 131495 AN XY: 695182

African (AFR) AF: 0.0599 AC: 1923 AN: 32116

American (AMR) AF: 0.0701 AC: 2759 AN: 39370

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 4862 AN: 23466

East Asian (EAS) AF: 0.000257 AC: 10 AN: 38970

South Asian (SAS) AF: 0.0488 AC: 3904 AN: 80076

European-Finnish (FIN) AF: 0.283 AC: 14597 AN: 51602

Middle Eastern (MID) AF: 0.0581 AC: 264 AN: 4542

European-Non Finnish (NFE) AF: 0.216 AC: 234240 AN: 1082964

Other (OTH) AF: 0.177 AC: 10263 AN: 58006

GnomAD4 genome AF: 0.151 AC: 22947 AN: 152042 Hom.: 2276 Cov.: 31 AF XY: 0.149 AC XY: 11095 AN XY: 74300

African (AFR) AF: 0.0659 AC: 2734 AN: 41488

American (AMR) AF: 0.0935 AC: 1430 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3470

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5166

South Asian (SAS) AF: 0.0318 AC: 153 AN: 4810

European-Finnish (FIN) AF: 0.275 AC: 2904 AN: 10570

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14583 AN: 67936

Other (OTH) AF: 0.127 AC: 269 AN: 2110

Alfa AF: 0.133 Hom.: 949

Bravo AF: 0.134

Asia WGS AF: 0.0300 AC: 103 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	-0.90
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs12912578; hg19: chr15-74473073; COSMIC: COSV51434996; COSMIC: COSV51434996;