rs7183244

Positions:

• chr15-67168973-T-C
• chr15-67168973-T-G

Variant summary

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

The NM_005902.4(SMAD3):​c.608-1581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 151,998 control chromosomes in the GnomAD database, including 37,737 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 0.70 (37737 hom., cov: 31)
• Consequence: SMAD3 NM_005902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD3	NM_005902.4	c.608-1581T>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.608-1581T>C		intron_variant		1	NM_005902.4	ENSP00000332973	P1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105850 AN: 151880 Hom.: 37688 Cov.: 31

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.697 AC: 105954 AN: 151998 Hom.: 37737 Cov.: 31 AF XY: 0.703 AC XY: 52206 AN XY: 74306

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.710

Alfa AF: 0.626 Hom.: 49384

Bravo AF: 0.716

Asia WGS AF: 0.723 AC: 2514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.30

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: rs7183244; hg19: chr15-67461311;