Genetic Variant SPEN-AS1:n.347+3999G>C (chr1-15788838-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000746505.1(SPEN-AS1):n.347+3999G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,794 control chromosomes in the GnomAD database, including 13,755 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 13755 hom., cov: 31)

Consequence

SPEN-AS1
ENST00000746505.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.454

Publications

6 publications found

Variant links:

COSMIC-nc: COSV60029099

Genes affected

SPEN-AS1 (HGNC:55937): (SPEN antisense RNA 1)

SPEN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
SPEN-AS1	ENST00000746505.1 link	n.347+3999G>C	intron_variant	Intron 3 of 3
SPEN-AS1	ENST00000746507.1 link	n.*74G>C	downstream_gene_variant
SPEN-AS1	ENST00000746508.1 link	n.*73G>C	downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63082

AN:

151676

Hom.:

13733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.407

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.0241

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.401

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

GnomAD4 genome

AF:

0.416

AC:

63151

AN:

151794

Hom.:

13755

Cov.:

AF XY:

0.414

AC XY:

30731

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.499

AC:

20635

AN:

41370

American (AMR)

AF:

0.407

AC:

6184

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

1390

AN:

3470

East Asian (EAS)

AF:

0.0240

AC:

124

AN:

5174

South Asian (SAS)

AF:

0.422

AC:

2031

AN:

4810

European-Finnish (FIN)

AF:

0.400

AC:

4205

AN:

10524

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.403

AC:

27390

AN:

67928

Other (OTH)

AF:

0.402

AC:

848

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1868

3736

5605

7473

9341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.301

Hom.:

885

Bravo

AF:

0.419

Asia WGS

AF:

0.262

AC:

913

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.33

PhyloP100

-0.45

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over