rs4886578

Variant names:

• chr15-74180694-C-T
• rs4886578
• NM_022369.4:c.1840+88G>A

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+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,511,048 control chromosomes in the GnomAD database, including 4,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (372 hom., cov: 32)
  • Exomes 𝑓: 0.062 (3639 hom.)
• Consequence: STRA6 NM_022369.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.405
• 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, 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=-0.84).
• BP6: Variant 15-74180694-C-T is Benign according to our data. Variant chr15-74180694-C-T is described in ClinVar as Benign. ClinVar VariationId is 1174449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.136 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+88G>A		intron	N/A	NP_071764.3
	STRA6	NM_001199042.2		c.1957+88G>A		intron	N/A	NP_001185971.1	Q9BX79-4
	STRA6	NM_001199040.2		c.1951+88G>A		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+88G>A		intron	N/A	ENSP00000378537.4	Q9BX79-1
	STRA6	ENST00000563965.5	TSL:1	c.1957+88G>A		intron	N/A	ENSP00000456609.1	Q9BX79-4
	STRA6	ENST00000423167.6	TSL:1	c.1813+88G>A		intron	N/A	ENSP00000413012.2	Q9BX79-3

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8479 AN: 152096 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0429

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.0621 AC: 84338 AN: 1358834 Hom.: 3639 AF XY: 0.0631 AC XY: 42003 AN XY: 665398

African (AFR) AF: 0.0108 AC: 329 AN: 30370

American (AMR) AF: 0.236 AC: 7375 AN: 31256

Ashkenazi Jewish (ASJ) AF: 0.0669 AC: 1364 AN: 20380

East Asian (EAS) AF: 0.114 AC: 4402 AN: 38632

South Asian (SAS) AF: 0.120 AC: 8539 AN: 70944

European-Finnish (FIN) AF: 0.0412 AC: 1993 AN: 48400

Middle Eastern (MID) AF: 0.0369 AC: 139 AN: 3770

European-Non Finnish (NFE) AF: 0.0534 AC: 56519 AN: 1059100

Other (OTH) AF: 0.0657 AC: 3678 AN: 55982

GnomAD4 genome AF: 0.0557 AC: 8481 AN: 152214 Hom.: 372 Cov.: 32 AF XY: 0.0573 AC XY: 4262 AN XY: 74422

African (AFR) AF: 0.0163 AC: 677 AN: 41540

American (AMR) AF: 0.141 AC: 2157 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3472

East Asian (EAS) AF: 0.116 AC: 601 AN: 5162

South Asian (SAS) AF: 0.116 AC: 560 AN: 4818

European-Finnish (FIN) AF: 0.0429 AC: 455 AN: 10614

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0530 AC: 3604 AN: 67990

Other (OTH) AF: 0.0506 AC: 107 AN: 2114

Alfa AF: 0.0575 Hom.: 459

Bravo AF: 0.0627

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.84
CADD	Benign	2.3
DANN	Benign	0.77
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4886578; hg19: chr15-74473035;