chr13-36848378-T-C

Position:

• chr13-36848378-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001127217.3(SMAD9):​c.*298A>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 0.0506 in 391,636 control chromosomes in the GnomAD database, including 1,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (637 hom., cov: 32)
  • Exomes 𝑓: 0.042 (467 hom.)
• Consequence: SMAD9 NM_001127217.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 13-36848378-T-C is Benign according to our data. Variant chr13-36848378-T-C is described in ClinVar as [Benign]. Clinvar id is 1280875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD9	NM_001127217.3	c.*298A>G		3_prime_UTR_variant	7/7	ENST00000379826.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD9	ENST00000379826.5	c.*298A>G		3_prime_UTR_variant	7/7	5	NM_001127217.3	P1
SMAD9	ENST00000350148.10	c.*298A>G		3_prime_UTR_variant	6/6	1

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9799 AN: 152088 Hom.: 622 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0559

GnomAD4 exome AF: 0.0416 AC: 9955 AN: 239430 Hom.: 467 Cov.: 0 AF XY: 0.0473 AC XY: 6006 AN XY: 126994

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0226

Gnomad4 ASJ exome AF: 0.0481

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0130

Gnomad4 NFE exome AF: 0.0174

Gnomad4 OTH exome AF: 0.0390

GnomAD4 genome AF: 0.0647 AC: 9853 AN: 152206 Hom.: 637 Cov.: 32 AF XY: 0.0665 AC XY: 4950 AN XY: 74426

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0139

Gnomad4 NFE AF: 0.0179

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0304 Hom.: 147

Bravo AF: 0.0670

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Nov 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.57

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: rs511674; hg19: chr13-37422515;