rs16953584

Positions:

• chr15-66723322-A-G

Variant summary

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

The NM_005585.5(SMAD6):​c.952+6824A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,174 control chromosomes in the GnomAD database, including 4,026 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 0.22 (4026 hom., cov: 32)
• Consequence: SMAD6 NM_005585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.954

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD6	NM_005585.5	c.952+6824A>G		intron_variant		ENST00000288840.10	NP_005576.3
SMAD6	XM_011521561.3	c.169+6824A>G		intron_variant			XP_011519863.1
SMAD6	NR_027654.2	n.2107+6182A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD6	ENST00000288840.10	c.952+6824A>G		intron_variant		1	NM_005585.5	ENSP00000288840.5
SMAD6	ENST00000557916.5	n.*67+6182A>G		intron_variant		1		ENSP00000452955.1
SMAD6	ENST00000559931.5	n.*67+6182A>G		intron_variant		3		ENSP00000453446.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33472 AN: 152056 Hom.: 4016 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.220 AC: 33502 AN: 152174 Hom.: 4026 Cov.: 32 AF XY: 0.224 AC XY: 16692 AN XY: 74400

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.250

Alfa AF: 0.212 Hom.: 7327

Bravo AF: 0.231

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.64

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: rs16953584; hg19: chr15-67015660;