dbSNP rs12913041: STRA6:c.1685-24T>C (chr15-74180961-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022369.4(STRA6):c.1685-24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,612,240 control chromosomes in the GnomAD database, including 32,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2273 hom., cov: 31)

Exomes 𝑓: 0.19 ( 30377 hom. )

Consequence

STRA6
NM_022369.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0960

Publications

3 publications found

Variant links:

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

STRA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 15-74180961-A-G is Benign according to our data. Variant chr15-74180961-A-G is described in ClinVar as Benign. ClinVar VariationId is 1239030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STRA6	NM_022369.4	MANE Select	c.1685-24T>C	intron	N/A	NP_071764.3
STRA6	NM_001199042.2		c.1802-24T>C	intron	N/A	NP_001185971.1	Q9BX79-4
STRA6	NM_001199040.2		c.1796-24T>C	intron	N/A	NP_001185969.1	Q9BX79-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STRA6	ENST00000395105.9	TSL:1 MANE Select	c.1685-24T>C	intron	N/A	ENSP00000378537.4	Q9BX79-1
STRA6	ENST00000563965.5	TSL:1	c.1802-24T>C	intron	N/A	ENSP00000456609.1	Q9BX79-4
STRA6	ENST00000423167.6	TSL:1	c.1658-24T>C	intron	N/A	ENSP00000413012.2	Q9BX79-3

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22970

AN:

151844

Hom.:

2270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0676

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0928

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.0332

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.127

GnomAD2 exomes

AF:

0.150

AC:

37314

AN:

249202

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.0656

Gnomad AMR exome

AF:

0.0684

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.275

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.192

AC:

280579

AN:

1460278

Hom.:

30377

Cov.:

AF XY:

0.188

AC XY:

136425

AN XY:

726264

show subpopulations

African (AFR)

AF:

0.0619

AC:

2073

AN:

33466

American (AMR)

AF:

0.0684

AC:

3057

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5392

AN:

26090

East Asian (EAS)

AF:

0.000252

AC:

AN:

39682

South Asian (SAS)

AF:

0.0489

AC:

4218

AN:

86188

European-Finnish (FIN)

AF:

0.283

AC:

14870

AN:

52618

Middle Eastern (MID)

AF:

0.0543

AC:

313

AN:

5764

European-Non Finnish (NFE)

AF:

0.216

AC:

239992

AN:

1111424

Other (OTH)

AF:

0.177

AC:

10654

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

11562

23124

34687

46249

57811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8036

16072

24108

32144

40180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.151

AC:

22979

AN:

151962

Hom.:

2273

Cov.:

AF XY:

0.150

AC XY:

11109

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0677

AC:

2807

AN:

41454

American (AMR)

AF:

0.0926

AC:

1416

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

725

AN:

3468

East Asian (EAS)

AF:

0.00136

AC:

AN:

5154

South Asian (SAS)

AF:

0.0324

AC:

156

AN:

4814

European-Finnish (FIN)

AF:

0.275

AC:

2907

AN:

10580

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.214

AC:

14555

AN:

67890

Other (OTH)

AF:

0.126

AC:

265

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

973

1946

2920

3893

4866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.186

Hom.:

600

Bravo

AF:

0.134

Asia WGS

AF:

0.0300

AC:

104

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.7

(source)

DANN

Benign

0.29

PhyloP100

0.096

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over