rs7183244

Variant names:

• chr15-67168973-T-C
• rs7183244
• NM_005902.4:c.608-1581T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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 Gene-Disease associations (from GenCC):

• aneurysm-osteoarthritis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMAD3	NM_005902.4	c.608-1581T>C		intron_variant	Intron 4 of 8	ENST00000327367.9	NP_005893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD3	ENST00000327367.9	c.608-1581T>C		intron_variant	Intron 4 of 8	1	NM_005902.4	ENSP00000332973.4

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

African (AFR) AF: 0.828 AC: 34337 AN: 41468

American (AMR) AF: 0.757 AC: 11558 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2434 AN: 3464

East Asian (EAS) AF: 0.772 AC: 3979 AN: 5156

South Asian (SAS) AF: 0.660 AC: 3180 AN: 4816

European-Finnish (FIN) AF: 0.662 AC: 6989 AN: 10554

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41213 AN: 67962

Other (OTH) AF: 0.710 AC: 1494 AN: 2104

Alfa AF: 0.648 Hom.: 92630

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
PhyloP100		-1.3
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: rs7183244; hg19: chr15-67461311;