chr15-66769129-C-T

Position:

• chr15-66769129-C-T

Variant summary

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

The NM_005585.5(SMAD6):​c.953-11868C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,932 control chromosomes in the GnomAD database, including 14,530 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 0.43 (14530 hom., cov: 31)
• Consequence: SMAD6 NM_005585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

Genes affected

SMAD6 (HGNC:6772): (SMAD family member 6) The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]

SMAD6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD6	NM_005585.5	c.953-11868C>T		intron_variant		ENST00000288840.10	NP_005576.3
SMAD6	XM_011521561.3	c.170-11868C>T		intron_variant			XP_011519863.1
SMAD6	NR_027654.2	n.2108-11868C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD6	ENST00000288840.10	c.953-11868C>T		intron_variant		1	NM_005585.5	ENSP00000288840.5
SMAD6	ENST00000557916.5	n.*68-11868C>T		intron_variant		1		ENSP00000452955.1
SMAD6	ENST00000559931.5	n.*68-11868C>T		intron_variant		3		ENSP00000453446.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64817 AN: 151814 Hom.: 14517 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.427 AC: 64854 AN: 151932 Hom.: 14530 Cov.: 31 AF XY: 0.432 AC XY: 32070 AN XY: 74256

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.453

Alfa AF: 0.450 Hom.: 3133

Bravo AF: 0.425

Asia WGS AF: 0.395 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.52

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: rs3934908; hg19: chr15-67061467;