rs3934907

Positions:

• chr15-66769097-C-A

Variant summary

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

The NM_005585.5(SMAD6):​c.953-11900C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,082 control chromosomes in the GnomAD database, including 4,185 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 0.21 (4185 hom., cov: 32)
• Consequence: SMAD6 NM_005585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

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]

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 (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD6	NM_005585.5	c.953-11900C>A		intron_variant		ENST00000288840.10
SMAD6	XM_011521561.3	c.170-11900C>A		intron_variant
SMAD6	NR_027654.2	n.2108-11900C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD6	ENST00000288840.10	c.953-11900C>A		intron_variant		1	NM_005585.5	P1
SMAD6	ENST00000557916.5	c.*68-11900C>A		intron_variant, NMD_transcript_variant		1
SMAD6	ENST00000559931.5	c.*68-11900C>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31614 AN: 151964 Hom.: 4169 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.208 AC: 31682 AN: 152082 Hom.: 4185 Cov.: 32 AF XY: 0.208 AC XY: 15447 AN XY: 74364

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.185

Alfa AF: 0.144 Hom.: 2381

Bravo AF: 0.217

Asia WGS AF: 0.317 AC: 1099 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	0.059
DANN	Benign	0.39

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: rs3934907; hg19: chr15-67061435;