rs1992215

chr15-67126599-G-A

Variant summary

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

The NM_005902.4(SMAD3):c.207-38296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,120 control chromosomes in the GnomAD database, including 35,369 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 0.68 (35369 hom., cov: 32)
• Consequence: SMAD3 NM_005902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD3	NM_005902.4	c.207-38296G>A		intron_variant		ENST00000327367.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD3	ENST00000327367.9	c.207-38296G>A		intron_variant		1	NM_005902.4	P1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103531 AN: 152002 Hom.: 35337 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.681 AC: 103622 AN: 152120 Hom.: 35369 Cov.: 32 AF XY: 0.676 AC XY: 50250 AN XY: 74358

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.675

Alfa AF: 0.672 Hom.: 66643

Bravo AF: 0.690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.5
Dann	Benign	0.39

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: rs1992215; hg19: chr15-67418937;