15-74207764-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001199041.2(STRA6):​c.-38C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,535,478 control chromosomes in the GnomAD database, including 47,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3647 hom., cov: 32)
Exomes 𝑓: 0.25 ( 43430 hom. )

Consequence

STRA6
NM_001199041.2 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.401
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]
CCDC33 (HGNC:26552): (coiled-coil domain containing 33) Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 15-74207764-G-A is Benign according to our data. Variant chr15-74207764-G-A is described in ClinVar as [Benign]. Clinvar id is 675105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STRA6NM_001199041.2 linkuse as main transcriptc.-38C>T 5_prime_UTR_premature_start_codon_gain_variant 1/19 NP_001185970.1 Q9BX79-6
STRA6NM_001199041.2 linkuse as main transcriptc.-38C>T 5_prime_UTR_variant 1/19 NP_001185970.1 Q9BX79-6
STRA6NM_001199040.2 linkuse as main transcriptc.96+1595C>T intron_variant NP_001185969.1 Q9BX79-5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STRA6ENST00000423167.6 linkuse as main transcriptc.-16+1036C>T intron_variant 1 ENSP00000413012.2 Q9BX79-3
STRA6ENST00000432245.6 linkuse as main transcriptc.-16+1036C>T intron_variant 1 ENSP00000407176.2 Q9BX79-2
STRA6ENST00000574278.5 linkuse as main transcriptc.-38C>T 5_prime_UTR_premature_start_codon_gain_variant 1/192 ENSP00000458827.1 Q9BX79-6

Frequencies

GnomAD3 genomes
AF:
0.203
AC:
30879
AN:
152020
Hom.:
3649
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0825
Gnomad AMI
AF:
0.232
Gnomad AMR
AF:
0.225
Gnomad ASJ
AF:
0.211
Gnomad EAS
AF:
0.281
Gnomad SAS
AF:
0.216
Gnomad FIN
AF:
0.239
Gnomad MID
AF:
0.290
Gnomad NFE
AF:
0.257
Gnomad OTH
AF:
0.225
GnomAD3 exomes
AF:
0.230
AC:
29562
AN:
128434
Hom.:
3629
AF XY:
0.233
AC XY:
16397
AN XY:
70320
show subpopulations
Gnomad AFR exome
AF:
0.0645
Gnomad AMR exome
AF:
0.204
Gnomad ASJ exome
AF:
0.227
Gnomad EAS exome
AF:
0.289
Gnomad SAS exome
AF:
0.213
Gnomad FIN exome
AF:
0.221
Gnomad NFE exome
AF:
0.260
Gnomad OTH exome
AF:
0.254
GnomAD4 exome
AF:
0.247
AC:
341834
AN:
1383338
Hom.:
43430
Cov.:
33
AF XY:
0.247
AC XY:
168545
AN XY:
682580
show subpopulations
Gnomad4 AFR exome
AF:
0.0733
Gnomad4 AMR exome
AF:
0.205
Gnomad4 ASJ exome
AF:
0.214
Gnomad4 EAS exome
AF:
0.308
Gnomad4 SAS exome
AF:
0.213
Gnomad4 FIN exome
AF:
0.221
Gnomad4 NFE exome
AF:
0.256
Gnomad4 OTH exome
AF:
0.234
GnomAD4 genome
AF:
0.203
AC:
30873
AN:
152140
Hom.:
3647
Cov.:
32
AF XY:
0.203
AC XY:
15100
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0823
Gnomad4 AMR
AF:
0.225
Gnomad4 ASJ
AF:
0.211
Gnomad4 EAS
AF:
0.280
Gnomad4 SAS
AF:
0.216
Gnomad4 FIN
AF:
0.239
Gnomad4 NFE
AF:
0.257
Gnomad4 OTH
AF:
0.221
Alfa
AF:
0.252
Hom.:
6864
Bravo
AF:
0.198
Asia WGS
AF:
0.235
AC:
817
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
1.5
DANN
Benign
0.65

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12915846; hg19: chr15-74500105; COSMIC: COSV60588118; COSMIC: COSV60588118; API