15-66702985-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005585.5(SMAD6):c.-274G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 313,182 control chromosomes in the GnomAD database, including 8,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3849 hom., cov: 32)
  • Exomes 𝑓: 0.24 (4957 hom.)
• Consequence: SMAD6 NM_005585.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.78

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 15-66702985-G-A is Benign according to our data. Variant chr15-66702985-G-A is described in ClinVar as [Benign]. Clinvar id is 1246802.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD6	NM_005585.5	c.-274G>A		5_prime_UTR_variant	1/4	ENST00000288840.10
SMAD6	NR_027654.2	n.750G>A		non_coding_transcript_exon_variant	1/5
SMAD6	XR_931827.3	n.750G>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD6	ENST00000288840.10	c.-274G>A		5_prime_UTR_variant	1/4	1	NM_005585.5	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34007 AN: 151834 Hom.: 3852 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.239 AC: 38600 AN: 161234 Hom.: 4957 Cov.: 0 AF XY: 0.242 AC XY: 19749 AN XY: 81448

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.224 AC: 34011 AN: 151948 Hom.: 3849 Cov.: 32 AF XY: 0.220 AC XY: 16370 AN XY: 74260

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.233

Alfa AF: 0.229 Hom.: 500

Bravo AF: 0.218

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	18
Dann	Benign	0.96

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: rs4776822; hg19: chr15-66995323;