15-67145753-A-G

Position:

• chr15-67145753-A-G

Variant summary

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

The NM_005902.4(SMAD3):​c.207-19142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,092 control chromosomes in the GnomAD database, including 36,088 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 0.67 (36088 hom., cov: 32)
• Consequence: SMAD3 NM_005902.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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]

ENSG00000259202 (HGNC:56692): (SMAD3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD3	NM_005902.4	c.207-19142A>G		intron_variant		ENST00000327367.9	NP_005893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD3	ENST00000327367.9	c.207-19142A>G		intron_variant		1	NM_005902.4	ENSP00000332973.4

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101889 AN: 151974 Hom.: 36083 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.670 AC: 101930 AN: 152092 Hom.: 36088 Cov.: 32 AF XY: 0.666 AC XY: 49473 AN XY: 74322

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.689

Alfa AF: 0.775 Hom.: 58844

Bravo AF: 0.648

Asia WGS AF: 0.500 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.71

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: rs893473; hg19: chr15-67438091;