NM_022369.4:c.406+111A>G

Variant names:

• chr15-74195897-T-C
• rs35255788
• NM_022369.4:c.406+111A>G

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.406+111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,475,066 control chromosomes in the GnomAD database, including 28,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2089 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26852 hom.)
• Consequence: STRA6 NM_022369.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.46
• Publications: 2 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=-0.9).
• BP6: Variant 15-74195897-T-C is Benign according to our data. Variant chr15-74195897-T-C is described in ClinVar as Benign. ClinVar VariationId is 1290883.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRA6	NM_022369.4	c.406+111A>G		intron_variant	Intron 5 of 18	ENST00000395105.9	NP_071764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9	c.406+111A>G		intron_variant	Intron 5 of 18	1	NM_022369.4	ENSP00000378537.4

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22139 AN: 151978 Hom.: 2089 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0880

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: 0.120

GnomAD4 exome AF: 0.190 AC: 251270 AN: 1322970 Hom.: 26852 AF XY: 0.186 AC XY: 121906 AN XY: 656884

African (AFR) AF: 0.0537 AC: 1634 AN: 30400

American (AMR) AF: 0.0678 AC: 2541 AN: 37492

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4382 AN: 23882

East Asian (EAS) AF: 0.000245 AC: 9 AN: 36788

South Asian (SAS) AF: 0.0469 AC: 3593 AN: 76654

European-Finnish (FIN) AF: 0.262 AC: 11335 AN: 43250

Middle Eastern (MID) AF: 0.0583 AC: 234 AN: 4014

European-Non Finnish (NFE) AF: 0.215 AC: 218134 AN: 1014894

Other (OTH) AF: 0.169 AC: 9408 AN: 55596

GnomAD4 genome AF: 0.146 AC: 22133 AN: 152096 Hom.: 2089 Cov.: 32 AF XY: 0.143 AC XY: 10644 AN XY: 74350

African (AFR) AF: 0.0621 AC: 2579 AN: 41518

American (AMR) AF: 0.0879 AC: 1342 AN: 15274

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

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5170

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

European-Finnish (FIN) AF: 0.258 AC: 2725 AN: 10576

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

European-Non Finnish (NFE) AF: 0.210 AC: 14284 AN: 67950

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

Alfa AF: 0.169 Hom.: 405

Bravo AF: 0.129

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.62
DANN	Benign	0.44
PhyloP100		-1.5
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: rs35255788; hg19: chr15-74488238;