15-67020117-T-C

Variant names:

• chr15-67020117-T-C
• rs16950516
• ENST00000558071.2:n.115-32470A>G

Variant summary

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

The NR_135686.1(SMAD3-DT):​n.1141-32470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,160 control chromosomes in the GnomAD database, including 2,056 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 0.15 (2056 hom., cov: 31)
• Consequence: SMAD3-DT NR_135686.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

Genes affected

ENSG00000259347 (HGNC:56759): (SMAD3 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD3-DT	NR_135686.1	n.1141-32470A>G		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000259347	ENST00000558071.2	n.115-32470A>G		intron_variant	Intron 1 of 4	5
ENSG00000259347	ENST00000692307.2	n.76-32855A>G		intron_variant	Intron 1 of 3
ENSG00000259347	ENST00000701435.1	n.117-32855A>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22275 AN: 152042 Hom.: 2058 Cov.: 31

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.146 AC: 22266 AN: 152160 Hom.: 2056 Cov.: 31 AF XY: 0.149 AC XY: 11085 AN XY: 74384

Gnomad4 AFR AF: 0.0388

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.150

Alfa AF: 0.134 Hom.: 388

Bravo AF: 0.131

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16950516; hg19: chr15-67312455;