rs266336

Positions:

• chr15-67029967-A-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.1140+29173T>C 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 0.836 in 152,254 control chromosomes in the GnomAD database, including 53,400 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 0.84 (53400 hom., cov: 33)
• Consequence: SMAD3-DT NR_135686.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD3-DT	NR_135686.1	n.1140+29173T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD3-DT	ENST00000701435.1	n.116+29173T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127224 AN: 152136 Hom.: 53336 Cov.: 33

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.836 AC: 127347 AN: 152254 Hom.: 53400 Cov.: 33 AF XY: 0.835 AC XY: 62127 AN XY: 74436

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.843

Alfa AF: 0.823 Hom.: 8720

Bravo AF: 0.849

Asia WGS AF: 0.794 AC: 2759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.2
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs266336; hg19: chr15-67322305;