13-36882104-G-T

Position:

• chr13-36882104-G-T

Variant summary

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

The NM_001127217.3(SMAD9):​c.-186-2229C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,364 control chromosomes in the GnomAD database, including 26,709 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 0.58 (26709 hom., cov: 31)
• Consequence: SMAD9 NM_001127217.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD9	NM_001127217.3	c.-186-2229C>A		intron_variant		ENST00000379826.5	NP_001120689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD9	ENST00000379826.5	c.-186-2229C>A		intron_variant		5	NM_001127217.3	ENSP00000369154	P1
SMAD9	ENST00000350148.10	c.-186-2229C>A		intron_variant		1		ENSP00000239885
SMAD9	ENST00000483941.2	n.254-2229C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88417 AN: 151246 Hom.: 26670 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.568

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.585 AC: 88511 AN: 151364 Hom.: 26709 Cov.: 31 AF XY: 0.583 AC XY: 43101 AN XY: 73932

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.579

Alfa AF: 0.531 Hom.: 31599

Bravo AF: 0.598

Asia WGS AF: 0.674 AC: 2341 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.44

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: rs648206; hg19: chr13-37456241;