13-36848476-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001127217.3(SMAD9):c.*200A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 608,684 control chromosomes in the GnomAD database, including 1,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (635 hom., cov: 32)
  • Exomes 𝑓: 0.042 (872 hom.)
• Consequence: SMAD9 NM_001127217.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 13-36848476-T-G is Benign according to our data. Variant chr13-36848476-T-G is described in ClinVar as [Benign]. Clinvar id is 1271459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD9	NM_001127217.3	c.*200A>C		3_prime_UTR_variant	7/7	ENST00000379826.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD9	ENST00000379826.5	c.*200A>C		3_prime_UTR_variant	7/7	5	NM_001127217.3	P1
SMAD9	ENST00000350148.10	c.*200A>C		3_prime_UTR_variant	6/6	1

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9796 AN: 152078 Hom.: 620 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0559

GnomAD4 exome AF: 0.0415 AC: 18952 AN: 456490 Hom.: 872 Cov.: 5 AF XY: 0.0453 AC XY: 10993 AN XY: 242656

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.0227

Gnomad4 ASJ exome AF: 0.0503

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0136

Gnomad4 NFE exome AF: 0.0184

Gnomad4 OTH exome AF: 0.0431

GnomAD4 genome AF: 0.0647 AC: 9851 AN: 152194 Hom.: 635 Cov.: 32 AF XY: 0.0664 AC XY: 4944 AN XY: 74420

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.0179

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0280 Hom.: 216

Bravo AF: 0.0672

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.016
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs489646; hg19: chr13-37422613;