Variant 15-66702985-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000288840.10(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
ENST00000288840.10 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.78

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SMAD6	NM_005585.5 linkuse as main transcript	c.-274G>A	5_prime_UTR_variant	1/4	ENST00000288840.10	NP_005576.3
SMAD6	NR_027654.2 linkuse as main transcript	n.750G>A	non_coding_transcript_exon_variant	1/5
SMAD6	XR_931827.3 linkuse as main transcript	n.750G>A	non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD6	ENST00000288840.10 linkuse as main transcript	c.-274G>A		5_prime_UTR_variant	1/4	1	NM_005585.5	ENSP00000288840	P1	O43541-1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34007

AN:

151834

Hom.:

3852

Cov.:

show subpopulations

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.:

AF XY:

0.242

AC XY:

19749

AN XY:

81448

show subpopulations

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.:

AF XY:

0.220

AC XY:

16370

AN XY:

74260

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over