Genetic Variant ENST00000297163.4:n.539A>T (chr5-136134352-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000297163.4(SMAD5-AS1):n.539A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,056 control chromosomes in the GnomAD database, including 10,847 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 0.36 ( 10845 hom., cov: 32)

Exomes 𝑓: 0.30 ( 2 hom. )

Consequence

SMAD5-AS1
ENST00000297163.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

9 publications found

Variant links:

Genes affected

SMAD5-AS1 (HGNC:30586): (SMAD5 antisense RNA 1) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

SMAD5-AS1 links:

SMAD5 (HGNC:6771): (SMAD family member 5) The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

SMAD5 links:

ENSG00000274934 (HGNC:):

ENSG00000274934 links:

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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=-0.67).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000297163.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMAD5	NM_005903.7	MANE Select	c.-245+1390T>A	intron	N/A	NP_005894.3
SMAD5-AS1	NR_026763.1		n.539A>T	non_coding_transcript_exon	Exon 1 of 2
SMAD5	NM_001001419.3		c.-329+1390T>A	intron	N/A	NP_001001419.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMAD5-AS1	ENST00000297163.4	TSL:1	n.539A>T	non_coding_transcript_exon	Exon 1 of 2
SMAD5	ENST00000545279.6	TSL:1 MANE Select	c.-245+1390T>A	intron	N/A	ENSP00000441954.2
SMAD5	ENST00000509297.6	TSL:1	c.-245+393T>A	intron	N/A	ENSP00000426696.2

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54683

AN:

151874

Hom.:

10816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.538

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.376

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.382

GnomAD4 exome

AF:

0.297

AC:

AN:

Hom.:

Cov.:

AF XY:

0.295

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.310

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.360

AC:

54758

AN:

151992

Hom.:

10845

Cov.:

AF XY:

0.356

AC XY:

26450

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.538

AC:

22304

AN:

41442

American (AMR)

AF:

0.284

AC:

4338

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1190

AN:

3466

East Asian (EAS)

AF:

0.377

AC:

1952

AN:

5172

South Asian (SAS)

AF:

0.187

AC:

899

AN:

4808

European-Finnish (FIN)

AF:

0.302

AC:

3183

AN:

10552

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19805

AN:

67960

Other (OTH)

AF:

0.384

AC:

811

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1735

3470

5206

6941

8676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.318

Hom.:

1058

Bravo

AF:

0.374

Asia WGS

AF:

0.343

AC:

1195

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.2

(source)

DANN

Benign

0.84

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over