dbSNP rs4585442: SMAD5:c.997+37A>G (chr5-136172692-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.997+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,358,494 control chromosomes in the GnomAD database, including 70,292 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 ( 10714 hom., cov: 33)

Exomes 𝑓: 0.31 ( 59578 hom. )

Consequence

SMAD5
NM_005903.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114

Publications

20 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD5	NM_005903.7 link	c.997+37A>G		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.997+37A>G		intron_variant	Intron 6 of 7	1	NM_005903.7	ENSP00000441954.2		Q99717

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54834

AN:

151942

Hom.:

10690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.386

GnomAD2 exomes

AF:

0.310

AC:

76384

AN:

246526

AF XY:

0.304

show subpopulations

Gnomad AFR exome

AF:

0.528

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.392

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.308

AC:

371346

AN:

1206432

Hom.:

59578

Cov.:

AF XY:

0.305

AC XY:

186770

AN XY:

613302

show subpopulations

African (AFR)

AF:

0.528

AC:

14951

AN:

28300

American (AMR)

AF:

0.256

AC:

11332

AN:

44308

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

8524

AN:

24350

East Asian (EAS)

AF:

0.366

AC:

14087

AN:

38512

South Asian (SAS)

AF:

0.214

AC:

17253

AN:

80700

European-Finnish (FIN)

AF:

0.310

AC:

16440

AN:

52966

Middle Eastern (MID)

AF:

0.346

AC:

1829

AN:

5288

European-Non Finnish (NFE)

AF:

0.307

AC:

270196

AN:

879942

Other (OTH)

AF:

0.321

AC:

16734

AN:

52066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

13127

26254

39380

52507

65634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8146

16292

24438

32584

40730

<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:

0.361

AC:

54902

AN:

152062

Hom.:

10714

Cov.:

AF XY:

0.357

AC XY:

26528

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.523

AC:

21701

AN:

41460

American (AMR)

AF:

0.286

AC:

4373

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1195

AN:

3462

East Asian (EAS)

AF:

0.377

AC:

1953

AN:

5184

South Asian (SAS)

AF:

0.211

AC:

1020

AN:

4824

European-Finnish (FIN)

AF:

0.305

AC:

3224

AN:

10568

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20335

AN:

67962

Other (OTH)

AF:

0.388

AC:

819

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1749

3497

5246

6994

8743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.384

Hom.:

4044

Bravo

AF:

0.373

Asia WGS

AF:

0.352

AC:

1226

AN:

3478

EpiCase

AF:

0.312

EpiControl

AF:

0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.9

(source)

DANN

Benign

0.30

PhyloP100

-0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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