Variant chr13-36848629-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127217.3(SMAD9):c.*47G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,583,340 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 125 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 101 hom. )

Consequence

SMAD9
NM_001127217.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.723

Variant links:

Genes affected

SMAD9 (HGNC:6774): (SMAD family member 9) The protein encoded by this gene is a member of the SMAD family, which transduces signals from TGF-beta family members. The encoded protein is activated by bone morphogenetic proteins and interacts with SMAD4. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

SMAD9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 13-36848629-C-T is Benign according to our data. Variant chr13-36848629-C-T is described in ClinVar as [Benign]. Clinvar id is 1232767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD9	NM_001127217.3 linkuse as main transcript	c.*47G>A		3_prime_UTR_variant	7/7	ENST00000379826.5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD9	ENST00000379826.5 linkuse as main transcript	c.*47G>A	3_prime_UTR_variant	7/7	5	NM_001127217.3	P1	O15198-1
SMAD9	ENST00000350148.10 linkuse as main transcript	c.*47G>A	3_prime_UTR_variant	6/6	1			O15198-2
SMAD9	ENST00000399275.7 linkuse as main transcript	c.*1050G>A	3_prime_UTR_variant, NMD_transcript_variant	6/6	1

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3270

AN:

152118

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0757

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00523

AC:

1315

AN:

251240

Hom.:

AF XY:

0.00368

AC XY:

499

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.0726

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00206

AC:

2947

AN:

1431104

Hom.:

101

Cov.:

AF XY:

0.00175

AC XY:

1247

AN XY:

713852

show subpopulations

Gnomad4 AFR exome

AF:

0.0739

Gnomad4 AMR exome

AF:

0.00354

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000379

Gnomad4 SAS exome

AF:

0.000257

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.00438

GnomAD4 genome

AF:

0.0216

AC:

3287

AN:

152236

Hom.:

125

Cov.:

AF XY:

0.0213

AC XY:

1584

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0759

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00423

Hom.:

Bravo

AF:

0.0239

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.9

DANN

Benign

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over