Genetic Variant ENSG00000267149:n.1001+5961T>C (chr19-55038944-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The XR_001754012.3(GP6-AS1):n.122-3856A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: XR_001754012.3 is not a MANE Select or MANE Plus Clinical transcript for GP6-AS1; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.813 (AC=123,695) in the gnomAD database across 152,064 control chromosomes, including 50,699 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.953. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.81 ( 50699 hom., cov: 31)

Consequence

GP6-AS1
XR_001754012.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.163

Publications

9 publications found

Variant links:

Genes affected

ENSG00000267149 (HGNC:):

ENSG00000267149 links:

GP6-AS1 (HGNC:55305): (GP6 antisense RNA 1)

GP6-AS1 links:

RDH13 (HGNC:19978): (retinol dehydrogenase 13) This gene encodes a mitochondrial short-chain dehydrogenase/reductase, which catalyzes the reduction and oxidation of retinoids. The encoded enzyme may function in retinoic acid production and may also protect the mitochondria against oxidative stress. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

RDH13 links:

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new If you want to explore the variant's impact on the transcript XR_001754012.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.9532 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000585492.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ENSG00000267149	ENST00000585492.1	TSL:2	n.1001+5961T>C	intron	N/A
GP6-AS1	ENST00000586845.1	TSL:3	n.134-3888A>G	intron	N/A
GP6-AS1	ENST00000586961.1	TSL:5	n.45-3888A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.814

AC:

123612

AN:

151946

Hom.:

50673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.854

Gnomad ASJ

AF:

0.772

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.805

Gnomad FIN

AF:

0.891

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.843

Gnomad OTH

AF:

0.825

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

GnomAD4 genome

AF:

0.813

AC:

123695

AN:

152064

Hom.:

50699

Cov.:

AF XY:

0.819

AC XY:

60852

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.715

AC:

29636

AN:

41444

American (AMR)

AF:

0.854

AC:

13012

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.772

AC:

2677

AN:

3468

East Asian (EAS)

AF:

0.976

AC:

5046

AN:

5172

South Asian (SAS)

AF:

0.805

AC:

3875

AN:

4816

European-Finnish (FIN)

AF:

0.891

AC:

9460

AN:

10612

Middle Eastern (MID)

AF:

0.850

AC:

250

AN:

294

European-Non Finnish (NFE)

AF:

0.843

AC:

57298

AN:

67994

Other (OTH)

AF:

0.825

AC:

1739

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1165

2329

3494

4658

5823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.824

Hom.:

75137

Bravo

AF:

0.805

Asia WGS

AF:

0.884

AC:

3074

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.981

AC:

120280

AN:

122656

Turkish Variome

AF:

0.828

AC:

1280

AN:

1546

Hom.:

537

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.980

AC:

8784

AN:

8960

Hom.:

4309

ABraOM SABE-WGS-1171

AF:

0.819

AC:

1919

AN:

2342

Hom.:

792

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.4

(source)

DANN

Benign

0.40

PhyloP100

-0.16

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over