chr15-67184430-C-T

Position:

• chr15-67184430-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005902.4(SMAD3):​c.872-297C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,046 control chromosomes in the GnomAD database, including 4,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4316 hom., cov: 32)
• Consequence: SMAD3 NM_005902.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.417

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-67184430-C-T is Benign according to our data. Variant chr15-67184430-C-T is described in ClinVar as [Benign]. Clinvar id is 683848.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD3	NM_005902.4	c.872-297C>T		intron_variant		ENST00000327367.9	NP_005893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD3	ENST00000327367.9	c.872-297C>T		intron_variant		1	NM_005902.4	ENSP00000332973.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34020 AN: 151928 Hom.: 4311 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.224 AC: 34060 AN: 152046 Hom.: 4316 Cov.: 32 AF XY: 0.228 AC XY: 16969 AN XY: 74296

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.249

Alfa AF: 0.193 Hom.: 762

Bravo AF: 0.229

Asia WGS AF: 0.342 AC: 1188 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.48

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: rs7181556; hg19: chr15-67476768;