rs11857410

Variant names:

• chr15-74196083-G-A
• rs11857410
• NM_022369.4:c.331C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022369.4(STRA6):​c.331C>T​(p.Leu111Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,613,882 control chromosomes in the GnomAD database, including 31,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2096 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29442 hom.)
• Consequence: STRA6 NM_022369.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.19
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 15-74196083-G-A is Benign according to our data. Variant chr15-74196083-G-A is described in ClinVar as Benign. ClinVar VariationId is 317117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.19 with no splicing effect.
• 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_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.331C>T	p.Leu111Leu	synonymous	Exon 5 of 19	NP_071764.3
	STRA6	NM_001199042.2		c.448C>T	p.Leu150Leu	synonymous	Exon 5 of 19	NP_001185971.1	Q9BX79-4
	STRA6	NM_001199040.2		c.442C>T	p.Leu148Leu	synonymous	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.331C>T	p.Leu111Leu	synonymous	Exon 5 of 19	ENSP00000378537.4	Q9BX79-1
	STRA6	ENST00000563965.5	TSL:1	c.448C>T	p.Leu150Leu	synonymous	Exon 5 of 19	ENSP00000456609.1	Q9BX79-4
	STRA6	ENST00000423167.6	TSL:1	c.304C>T	p.Leu102Leu	synonymous	Exon 5 of 19	ENSP00000413012.2	Q9BX79-3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22151 AN: 152026 Hom.: 2096 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.145 AC: 36275 AN: 250618 AF XY: 0.144

Gnomad AFR exome AF: 0.0614

Gnomad AMR exome AF: 0.0655

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.189 AC: 276193 AN: 1461738 Hom.: 29442 Cov.: 33 AF XY: 0.185 AC XY: 134226 AN XY: 727152

African (AFR) AF: 0.0534 AC: 1787 AN: 33478

American (AMR) AF: 0.0669 AC: 2993 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4841 AN: 26134

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39700

South Asian (SAS) AF: 0.0472 AC: 4074 AN: 86252

European-Finnish (FIN) AF: 0.264 AC: 14066 AN: 53334

Middle Eastern (MID) AF: 0.0512 AC: 295 AN: 5766

European-Non Finnish (NFE) AF: 0.214 AC: 237850 AN: 1111968

Other (OTH) AF: 0.170 AC: 10276 AN: 60386

GnomAD4 genome AF: 0.146 AC: 22147 AN: 152144 Hom.: 2096 Cov.: 32 AF XY: 0.143 AC XY: 10654 AN XY: 74382

African (AFR) AF: 0.0622 AC: 2583 AN: 41520

American (AMR) AF: 0.0877 AC: 1341 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 650 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4822

European-Finnish (FIN) AF: 0.258 AC: 2733 AN: 10590

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

European-Non Finnish (NFE) AF: 0.210 AC: 14289 AN: 67952

Other (OTH) AF: 0.118 AC: 250 AN: 2112

Alfa AF: 0.177 Hom.: 8883

Bravo AF: 0.129

Asia WGS AF: 0.0270 AC: 92 AN: 3478

EpiCase AF: 0.186

EpiControl AF: 0.182

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
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.9
DANN	Benign	0.74
PhyloP100		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs11857410; hg19: chr15-74488424; COSMIC: COSV60584425; COSMIC: COSV60584425;