rs34147822

Variant names:

• chr15-74195911-T-C
• rs34147822
• NM_022369.4:c.406+97A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-74195911-T-C
• chr15-74195911-T-G

Variant summary

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

The NM_001199042.2(STRA6):​c.523+97A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,543,162 control chromosomes in the GnomAD database, including 30,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2040 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28034 hom.)
• Consequence: STRA6 NM_001199042.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.265
• 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: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.82).
• BP6: Variant 15-74195911-T-C is Benign according to our data. Variant chr15-74195911-T-C is described in ClinVar as Benign. ClinVar VariationId is 1288646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199042.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	NM_022369.4	MANE Select	c.406+97A>G		intron	N/A	NP_071764.3
	STRA6	NM_001199042.2		c.523+97A>G		intron	N/A	NP_001185971.1
	STRA6	NM_001199040.2		c.517+97A>G		intron	N/A	NP_001185969.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	ENST00000395105.9	TSL:1 MANE Select	c.406+97A>G		intron	N/A	ENSP00000378537.4
	STRA6	ENST00000563965.5	TSL:1	c.523+97A>G		intron	N/A	ENSP00000456609.1
	STRA6	ENST00000423167.6	TSL:1	c.379+97A>G		intron	N/A	ENSP00000413012.2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21371 AN: 152066 Hom.: 2040 Cov.: 32

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0861

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.189 AC: 262792 AN: 1390978 Hom.: 28034 AF XY: 0.185 AC XY: 127616 AN XY: 690542

African (AFR) AF: 0.0361 AC: 1154 AN: 31990

American (AMR) AF: 0.0667 AC: 2692 AN: 40364

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4609 AN: 24984

East Asian (EAS) AF: 0.000237 AC: 9 AN: 38038

South Asian (SAS) AF: 0.0469 AC: 3780 AN: 80560

European-Finnish (FIN) AF: 0.263 AC: 12194 AN: 46438

Middle Eastern (MID) AF: 0.0552 AC: 236 AN: 4276

European-Non Finnish (NFE) AF: 0.214 AC: 228322 AN: 1066342

Other (OTH) AF: 0.169 AC: 9796 AN: 57986

GnomAD4 genome AF: 0.140 AC: 21369 AN: 152184 Hom.: 2040 Cov.: 32 AF XY: 0.138 AC XY: 10286 AN XY: 74400

African (AFR) AF: 0.0444 AC: 1843 AN: 41538

American (AMR) AF: 0.0860 AC: 1315 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 651 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.0320 AC: 154 AN: 4818

European-Finnish (FIN) AF: 0.258 AC: 2730 AN: 10594

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

European-Non Finnish (NFE) AF: 0.210 AC: 14289 AN: 67980

Other (OTH) AF: 0.113 AC: 239 AN: 2114

Alfa AF: 0.180 Hom.: 392

Bravo AF: 0.124

Asia WGS AF: 0.0250 AC: 86 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	-0.82
CADD	Benign	3.7
DANN	Benign	0.60
PhyloP100		-0.27
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: rs34147822; hg19: chr15-74488252;