chr15-74194103-C-T

Variant names:

• chr15-74194103-C-T
• rs974456
• NM_022369.4:c.598-181G>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.598-181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,906 control chromosomes in the GnomAD database, including 10,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.35 (10388 hom., cov: 31)
• Consequence: STRA6 NM_022369.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.00
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-74194103-C-T is Benign according to our data. Variant chr15-74194103-C-T is described in ClinVar as Benign. ClinVar VariationId is 1285943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 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.598-181G>A		intron	N/A	NP_071764.3
	STRA6	NM_001199042.2		c.715-181G>A		intron	N/A	NP_001185971.1	Q9BX79-4
	STRA6	NM_001199040.2		c.709-181G>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.598-181G>A		intron	N/A	ENSP00000378537.4	Q9BX79-1
	STRA6	ENST00000563965.5	TSL:1	c.715-181G>A		intron	N/A	ENSP00000456609.1	Q9BX79-4
	STRA6	ENST00000423167.6	TSL:1	c.571-181G>A		intron	N/A	ENSP00000413012.2	Q9BX79-3

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52986 AN: 151788 Hom.: 10356 Cov.: 31

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.349 AC: 53063 AN: 151906 Hom.: 10388 Cov.: 31 AF XY: 0.350 AC XY: 25985 AN XY: 74252

African (AFR) AF: 0.533 AC: 22056 AN: 41382

American (AMR) AF: 0.284 AC: 4342 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 942 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1900 AN: 5154

South Asian (SAS) AF: 0.264 AC: 1268 AN: 4802

European-Finnish (FIN) AF: 0.355 AC: 3748 AN: 10548

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17943 AN: 67958

Other (OTH) AF: 0.289 AC: 610 AN: 2112

Alfa AF: 0.272 Hom.: 7225

Bravo AF: 0.354

Asia WGS AF: 0.339 AC: 1179 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	0.26
DANN	Benign	0.41
PhyloP100		-2.0
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: rs974456; hg19: chr15-74486444;