rs17293443

Variant names:

• chr15-67145525-T-C
• rs17293443
• NM_005902.4:c.207-19370T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005902.4(SMAD3):​c.207-19370T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,236 control chromosomes in the GnomAD database, including 2,593 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 0.17 (2593 hom., cov: 32)
• Consequence: SMAD3 NM_005902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 30 publications found

Genes affected

SMAD3 (HGNC:6769): (SMAD family member 3) The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022]

SMAD3-AS1 (HGNC:56692): (SMAD3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005902.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD3	NM_005902.4	MANE Select	c.207-19370T>C		intron	N/A	NP_005893.1	P84022-1
	SMAD3	NM_001407011.1		c.207-19370T>C		intron	N/A	NP_001393940.1	H3BQ00
	SMAD3	NM_001145103.2		c.74+7425T>C		intron	N/A	NP_001138575.1	P84022-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD3	ENST00000327367.9	TSL:1 MANE Select	c.207-19370T>C		intron	N/A	ENSP00000332973.4	P84022-1
	SMAD3	ENST00000439724.7	TSL:1	c.74+7425T>C		intron	N/A	ENSP00000401133.3	P84022-2
	SMAD3	ENST00000540846.6	TSL:1	c.-109-19370T>C		intron	N/A	ENSP00000437757.2	P84022-3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25571 AN: 152116 Hom.: 2595 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.168 AC: 25558 AN: 152236 Hom.: 2593 Cov.: 32 AF XY: 0.167 AC XY: 12399 AN XY: 74428

African (AFR) AF: 0.0623 AC: 2590 AN: 41554

American (AMR) AF: 0.151 AC: 2313 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 758 AN: 3470

East Asian (EAS) AF: 0.0619 AC: 321 AN: 5188

South Asian (SAS) AF: 0.111 AC: 537 AN: 4822

European-Finnish (FIN) AF: 0.267 AC: 2825 AN: 10584

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15593 AN: 68010

Other (OTH) AF: 0.166 AC: 350 AN: 2110

Alfa AF: 0.206 Hom.: 7427

Bravo AF: 0.155

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.76
PhyloP100		-0.038
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17293443; hg19: chr15-67437863;