dbSNP rs4146185: SMAD5:c.998-32T>A (chr5-136174344-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 NM_005903.7(SMAD5):c.998-32T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,597,872 control chromosomes in the GnomAD database, including 78,574 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 ( 10569 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68005 hom. )

Consequence

SMAD5
NM_005903.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.268

Publications

9 publications found

Variant links:

Genes affected

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:

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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD5	NM_005903.7 link	c.998-32T>A		intron_variant	Intron 6 of 7	ENST00000545279.6	NP_005894.3	Q99717Q68DB7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6 link	c.998-32T>A		intron_variant	Intron 6 of 7	1	NM_005903.7	ENSP00000441954.2		Q99717

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54174

AN:

151872

Hom.:

10541

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:

0.375

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.382

GnomAD2 exomes

AF:

0.302

AC:

74238

AN:

245512

AF XY:

0.296

show subpopulations

Gnomad AFR exome

AF:

0.532

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.312

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

AF:

0.301

AC:

435139

AN:

1445882

Hom.:

68005

Cov.:

AF XY:

0.297

AC XY:

213372

AN XY:

717958

show subpopulations

African (AFR)

AF:

0.533

AC:

17623

AN:

33046

American (AMR)

AF:

0.253

AC:

11259

AN:

44454

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

8985

AN:

25944

East Asian (EAS)

AF:

0.364

AC:

14362

AN:

39440

South Asian (SAS)

AF:

0.185

AC:

15906

AN:

85804

European-Finnish (FIN)

AF:

0.308

AC:

16396

AN:

53226

Middle Eastern (MID)

AF:

0.330

AC:

1895

AN:

5742

European-Non Finnish (NFE)

AF:

0.300

AC:

329961

AN:

1098446

Other (OTH)

AF:

0.314

AC:

18752

AN:

59780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

13941

27882

41823

55764

69705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11088

22176

33264

44352

55440

<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:

54247

AN:

151990

Hom.:

10569

Cov.:

AF XY:

0.352

AC XY:

26178

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.527

AC:

21848

AN:

41432

American (AMR)

AF:

0.282

AC:

4301

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1189

AN:

3468

East Asian (EAS)

AF:

0.376

AC:

1942

AN:

5164

South Asian (SAS)

AF:

0.183

AC:

885

AN:

4824

European-Finnish (FIN)

AF:

0.301

AC:

3184

AN:

10566

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19813

AN:

67956

Other (OTH)

AF:

0.384

AC:

809

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1698

3395

5093

6790

8488

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:

0.317

Hom.:

1522

Bravo

AF:

0.370

Asia WGS

AF:

0.341

AC:

1189

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.90

(source)

DANN

Benign

0.45

PhyloP100

-0.27

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over