rs576434

Positions:

• chr13-36884002-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127217.3(SMAD9):​c.-186-4127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,898 control chromosomes in the GnomAD database, including 14,327 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 0.43 (14327 hom., cov: 31)
• Consequence: SMAD9 NM_001127217.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.600

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD9	NM_001127217.3	c.-186-4127A>G		intron_variant		ENST00000379826.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD9	ENST00000379826.5	c.-186-4127A>G		intron_variant		5	NM_001127217.3	P1
SMAD9	ENST00000350148.10	c.-186-4127A>G		intron_variant		1
SMAD9	ENST00000483941.2	n.254-4127A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65657 AN: 151780 Hom.: 14307 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.442

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.433 AC: 65725 AN: 151898 Hom.: 14327 Cov.: 31 AF XY: 0.429 AC XY: 31834 AN XY: 74232

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.446

Alfa AF: 0.435 Hom.: 7253

Bravo AF: 0.438

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.1
DANN	Benign	0.62

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: rs576434; hg19: chr13-37458139;