15-67150258-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The NM_005902.4(SMAD3):c.207-14637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,144 control chromosomes in the GnomAD database, including 2,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2806 hom., cov: 32)
• Consequence: SMAD3 NM_005902.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 15-67150258-C-T is Benign according to our data. Variant chr15-67150258-C-T is described in ClinVar as [Benign]. Clinvar id is 811543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD3	NM_005902.4	c.207-14637C>T		intron_variant		ENST00000327367.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD3	ENST00000327367.9	c.207-14637C>T		intron_variant		1	NM_005902.4	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26271 AN: 152026 Hom.: 2810 Cov.: 32

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.173 AC: 26259 AN: 152144 Hom.: 2806 Cov.: 32 AF XY: 0.172 AC XY: 12821 AN XY: 74374

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0276

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.175

Alfa AF: 0.211 Hom.: 4360

Bravo AF: 0.160

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Aneurysm-osteoarthritis syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 25, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
Cadd	Benign	22
Dann	Uncertain	0.98

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: rs17293632; hg19: chr15-67442596;