Genetic Variant ENST00000658284.2:n.531-2198A>G (chr4-145447634-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000658284.2(SMAD1-AS2):n.531-2198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 150,960 control chromosomes in the GnomAD database, including 9,068 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 0.31 ( 9068 hom., cov: 32)

Consequence

SMAD1-AS2
ENST00000658284.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.935

Publications

2 publications found

Variant links:

Genes affected

SMAD1-AS2 (HGNC:49381): (SMAD1 antisense RNA 2)

SMAD1-AS2 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
SMAD1-AS2	ENST00000658284.2 link	n.531-2198A>G	intron_variant	Intron 3 of 3
SMAD1-AS2	ENST00000813541.1 link	n.496+20845A>G	intron_variant	Intron 4 of 4
SMAD1-AS2	ENST00000813542.1 link	n.454+20845A>G	intron_variant	Intron 3 of 3
SMAD1-AS2	ENST00000813543.1 link	n.628-2198A>G	intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47178

AN:

150842

Hom.:

9066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.0993

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.311

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

GnomAD4 genome

AF:

0.313

AC:

47179

AN:

150960

Hom.:

9068

Cov.:

AF XY:

0.309

AC XY:

22811

AN XY:

73740

show subpopulations

African (AFR)

AF:

0.106

AC:

4280

AN:

40514

American (AMR)

AF:

0.250

AC:

3810

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1053

AN:

3466

East Asian (EAS)

AF:

0.0985

AC:

509

AN:

5166

South Asian (SAS)

AF:

0.297

AC:

1415

AN:

4766

European-Finnish (FIN)

AF:

0.457

AC:

4819

AN:

10548

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.444

AC:

30165

AN:

67968

Other (OTH)

AF:

0.308

AC:

648

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1527

3054

4581

6108

7635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.367

Hom.:

1513

Bravo

AF:

0.283

Asia WGS

AF:

0.180

AC:

627

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.4

(source)

DANN

Benign

0.81

PhyloP100

0.94

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