13-36849084-C-G

Position:

• chr13-36849084-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001127217.3(SMAD9):​c.1261-265G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 152,358 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0051 (3 hom., cov: 32)
• Consequence: SMAD9 NM_001127217.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.565

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=-0.83).
• BP6: Variant 13-36849084-C-G is Benign according to our data. Variant chr13-36849084-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1207558.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00512 (780/152358) while in subpopulation AMR AF= 0.00673 (103/15312). AF 95% confidence interval is 0.00571. There are 3 homozygotes in gnomad4. There are 393 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 780 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD9	NM_001127217.3	c.1261-265G>C		intron_variant		ENST00000379826.5	NP_001120689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD9	ENST00000379826.5	c.1261-265G>C		intron_variant		5	NM_001127217.3	ENSP00000369154.4
SMAD9	ENST00000350148.10	c.1150-265G>C		intron_variant		1		ENSP00000239885.6
SMAD9	ENST00000399275.7	n.*860-265G>C		intron_variant		1		ENSP00000382216.3

Frequencies

GnomAD3 genomes AF: 0.00512 AC: 780 AN: 152240 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00620

Gnomad OTH AF: 0.00813

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

GnomAD4 genome AF: 0.00512 AC: 780 AN: 152358 Hom.: 3 Cov.: 32 AF XY: 0.00528 AC XY: 393 AN XY: 74494

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00673

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.00620

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00492 Hom.: 0

Bravo AF: 0.00479

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.73

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: rs61950365; hg19: chr13-37423221;