rs17293443

Positions:

• chr15-67145525-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD3	NM_005902.4	c.207-19370T>C		intron_variant		ENST00000327367.9	NP_005893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD3	ENST00000327367.9	c.207-19370T>C		intron_variant		1	NM_005902.4	ENSP00000332973	P1
SMAD3-AS1	ENST00000558463.1	n.119+526A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0619

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.166

Alfa AF: 0.210 Hom.: 5199

Bravo AF: 0.155

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.76

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: rs17293443; hg19: chr15-67437863;