rs11858577

chr15-66774225-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.953-6772C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,194 control chromosomes in the GnomAD database, including 942 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 0.10 (942 hom., cov: 32)
• Consequence: SMAD6 NM_005585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD6	NM_005585.5	c.953-6772C>T		intron_variant		ENST00000288840.10
SMAD6	XM_011521561.3	c.170-6772C>T		intron_variant
SMAD6	NR_027654.2	n.2108-6772C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD6	ENST00000288840.10	c.953-6772C>T		intron_variant		1	NM_005585.5	P1
SMAD6	ENST00000557916.5	c.*68-6772C>T		intron_variant, NMD_transcript_variant		1
SMAD6	ENST00000559931.5	c.*68-6772C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15576 AN: 152076 Hom.: 941 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0600

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.0661

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0949

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.0905

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

GnomAD4 genome AF: 0.102 AC: 15592 AN: 152194 Hom.: 942 Cov.: 32 AF XY: 0.103 AC XY: 7678 AN XY: 74398

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0599

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.0662

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0949

Gnomad4 NFE AF: 0.0804

Gnomad4 OTH AF: 0.0910

Alfa AF: 0.0808 Hom.: 1100

Bravo AF: 0.102

Asia WGS AF: 0.0870 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	11
Dann	Benign	0.95

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: rs11858577; hg19: chr15-67066563;