Genetic Variant ENST00000297163.4:n.1053A>C (chr5-136133838-T-G) – 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.1053A>C 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 0.357 in 154,388 control chromosomes in the GnomAD database, including 10,723 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 ( 10558 hom., cov: 30)

Exomes 𝑓: 0.34 ( 165 hom. )

Consequence

SMAD5-AS1
ENST00000297163.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.371

Publications

22 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:

ENSG00000277524 (HGNC:):

ENSG00000277524 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=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 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+876T>G	intron	N/A	NP_005894.3
SMAD5-AS1	NR_026763.1		n.1053A>C	non_coding_transcript_exon	Exon 1 of 2
SMAD5	NM_001001419.3		c.-329+876T>G	intron	N/A	NP_001001419.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMAD5-AS1	ENST00000297163.4	TSL:1	n.1053A>C	non_coding_transcript_exon	Exon 1 of 2
SMAD5	ENST00000509297.6	TSL:1	c.-366T>G	5_prime_UTR	Exon 1 of 8	ENSP00000426696.2
SMAD5	ENST00000545279.6	TSL:1 MANE Select	c.-245+876T>G	intron	N/A	ENSP00000441954.2

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54098

AN:

151566

Hom.:

10530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.381

GnomAD4 exome

AF:

0.336

AC:

908

AN:

2702

Hom.:

165

Cov.:

AF XY:

0.335

AC XY:

461

AN XY:

1378

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.198

AC:

AN:

European-Finnish (FIN)

AF:

0.303

AC:

175

AN:

578

Middle Eastern (MID)

AF:

0.359

AC:

582

AN:

1622

European-Non Finnish (NFE)

AF:

0.185

AC:

AN:

Other (OTH)

AF:

0.324

AC:

AN:

256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.357

AC:

54172

AN:

151686

Hom.:

10558

Cov.:

AF XY:

0.353

AC XY:

26139

AN XY:

74086

show subpopulations

African (AFR)

AF:

0.528

AC:

21811

AN:

41346

American (AMR)

AF:

0.282

AC:

4294

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1190

AN:

3470

East Asian (EAS)

AF:

0.375

AC:

1922

AN:

5132

South Asian (SAS)

AF:

0.187

AC:

898

AN:

4792

European-Finnish (FIN)

AF:

0.303

AC:

3181

AN:

10502

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19793

AN:

67892

Other (OTH)

AF:

0.383

AC:

807

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

1688

3376

5064

6752

8440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.295

Hom.:

5705

Bravo

AF:

0.370

Asia WGS

AF:

0.342

AC:

1192

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.37

PromoterAI

0.035

Neutral

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over