rs7182227

Positions:

• chr15-66741083-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005585.5(SMAD6):​c.952+24585C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,284 control chromosomes in the GnomAD database, including 1,397 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 0.12 (1397 hom., cov: 33)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: SMAD6 NM_005585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.801

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD6	NM_005585.5	c.952+24585C>T		intron_variant		ENST00000288840.10	NP_005576.3
SMAD6	XM_011521561.3	c.169+24585C>T		intron_variant			XP_011519863.1
SMAD6	NR_027654.2	n.2107+23943C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD6	ENST00000288840.10	c.952+24585C>T		intron_variant		1	NM_005585.5	ENSP00000288840	P1
	ENST00000612806.1	n.639C>T		non_coding_transcript_exon_variant	1/1
SMAD6	ENST00000557916.5	c.*67+23943C>T		intron_variant, NMD_transcript_variant		1		ENSP00000452955
SMAD6	ENST00000559931.5	c.*67+23943C>T		intron_variant, NMD_transcript_variant		3		ENSP00000453446

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18415 AN: 152158 Hom.: 1393 Cov.: 33

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0926

Gnomad SAS AF: 0.0881

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.121 AC: 18424 AN: 152276 Hom.: 1397 Cov.: 33 AF XY: 0.123 AC XY: 9123 AN XY: 74466

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0928

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.130

Alfa AF: 0.133 Hom.: 394

Bravo AF: 0.127

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Benign	0.88

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: rs7182227; hg19: chr15-67033421;