dbSNP rs12719481: SMAD5:c.*887A>G (chr5-136178367-A-G) – 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.*887A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,514 control chromosomes in the GnomAD database, including 10,603 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 ( 10581 hom., cov: 33)

Exomes 𝑓: 0.32 ( 22 hom. )

Consequence

SMAD5
NM_005903.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Publications

15 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=-0.73).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005903.7. 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.*887A>G	3_prime_UTR	Exon 8 of 8	NP_005894.3
SMAD5	NM_001001419.3		c.*887A>G	3_prime_UTR	Exon 9 of 9	NP_001001419.1
SMAD5	NM_001001420.3		c.*887A>G	3_prime_UTR	Exon 7 of 7	NP_001001420.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMAD5	ENST00000545279.6	TSL:1 MANE Select	c.*887A>G	3_prime_UTR	Exon 8 of 8	ENSP00000441954.2
SMAD5	ENST00000545620.5	TSL:5	c.*887A>G	3_prime_UTR	Exon 7 of 7	ENSP00000446474.2
SMAD5	ENST00000513418.1	TSL:5	n.162+3735A>G	intron	N/A	ENSP00000427650.1

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54238

AN:

151966

Hom.:

10553

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:

0.376

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.383

GnomAD4 exome

AF:

0.316

AC:

136

AN:

430

Hom.:

Cov.:

AF XY:

0.341

AC XY:

AN XY:

258

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:

0.318

AC:

135

AN:

424

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: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.357

AC:

54311

AN:

152084

Hom.:

10581

Cov.:

AF XY:

0.353

AC XY:

26242

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.527

AC:

21859

AN:

41476

American (AMR)

AF:

0.282

AC:

4309

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1189

AN:

3468

East Asian (EAS)

AF:

0.377

AC:

1951

AN:

5172

South Asian (SAS)

AF:

0.185

AC:

892

AN:

4822

European-Finnish (FIN)

AF:

0.302

AC:

3189

AN:

10572

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19833

AN:

67970

Other (OTH)

AF:

0.385

AC:

813

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1741

3482

5224

6965

8706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.320

Hom.:

10586

Bravo

AF:

0.370

Asia WGS

AF:

0.341

AC:

1188

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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