15-67029048-T-C

Variant summary

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

The NR_135686.1(SMAD3-DT):n.1140+30092A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 151,982 control chromosomes in the GnomAD database, including 33,515 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 0.66 (33515 hom., cov: 31)
• Consequence: SMAD3-DT NR_135686.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

Genes affected

SMAD3-DT (HGNC:56759): (SMAD3 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD3-DT	NR_135686.1	n.1140+30092A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD3-DT	ENST00000701435.1	n.116+30092A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100653 AN: 151864 Hom.: 33489 Cov.: 31

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.663 AC: 100719 AN: 151982 Hom.: 33515 Cov.: 31 AF XY: 0.664 AC XY: 49290 AN XY: 74268

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.669

Alfa AF: 0.670 Hom.: 7274

Bravo AF: 0.676

Asia WGS AF: 0.555 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.5
Dann	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7178347; hg19: chr15-67321386;