dbSNP rs1109158: SMAD5:c.775+131T>A (chr5-136163522-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.775+131T>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 611,336 control chromosomes in the GnomAD database, including 31,128 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 ( 10442 hom., cov: 32)

Exomes 𝑓: 0.29 ( 20686 hom. )

Consequence

SMAD5
NM_005903.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.103

Publications

7 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 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.775+131T>A	intron	N/A	NP_005894.3
SMAD5	NM_001001419.3		c.775+131T>A	intron	N/A	NP_001001419.1
SMAD5	NM_001001420.3		c.775+131T>A	intron	N/A	NP_001001420.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMAD5	ENST00000545279.6	TSL:1 MANE Select	c.775+131T>A	intron	N/A	ENSP00000441954.2
SMAD5	ENST00000509297.6	TSL:1	c.775+131T>A	intron	N/A	ENSP00000426696.2
SMAD5	ENST00000545620.5	TSL:5	c.775+131T>A	intron	N/A	ENSP00000446474.2

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53965

AN:

151924

Hom.:

10420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.521

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.382

GnomAD4 exome

AF:

0.290

AC:

133132

AN:

459294

Hom.:

20686

AF XY:

0.287

AC XY:

67336

AN XY:

235026

show subpopulations

African (AFR)

AF:

0.524

AC:

5322

AN:

10152

American (AMR)

AF:

0.276

AC:

2932

AN:

10630

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

4036

AN:

11806

East Asian (EAS)

AF:

0.356

AC:

9049

AN:

25406

South Asian (SAS)

AF:

0.185

AC:

4654

AN:

25198

European-Finnish (FIN)

AF:

0.307

AC:

11158

AN:

36334

Middle Eastern (MID)

AF:

0.318

AC:

598

AN:

1882

European-Non Finnish (NFE)

AF:

0.280

AC:

87856

AN:

313532

Other (OTH)

AF:

0.309

AC:

7527

AN:

24354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

4367

8735

13102

17470

21837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1532

3064

4596

6128

7660

<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:

0.355

AC:

54031

AN:

152042

Hom.:

10442

Cov.:

AF XY:

0.351

AC XY:

26100

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.522

AC:

21611

AN:

41434

American (AMR)

AF:

0.281

AC:

4298

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1190

AN:

3470

East Asian (EAS)

AF:

0.376

AC:

1946

AN:

5170

South Asian (SAS)

AF:

0.185

AC:

892

AN:

4826

European-Finnish (FIN)

AF:

0.301

AC:

3184

AN:

10566

Middle Eastern (MID)

AF:

0.363

AC:

106

AN:

292

European-Non Finnish (NFE)

AF:

0.292

AC:

19825

AN:

67972

Other (OTH)

AF:

0.384

AC:

811

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1694

3388

5081

6775

8469

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:

0.315

Hom.:

1029

Bravo

AF:

0.368

Asia WGS

AF:

0.340

AC:

1186

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.4

(source)

DANN

Benign

0.43

PhyloP100

0.10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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