Variant rs12591946 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005585.5(SMAD6):c.1167C>T(p.Phe389=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00611 in 1,608,378 control chromosomes in the GnomAD database, including 625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 94 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 531 hom. )

Consequence

SMAD6
NM_005585.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0830

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 15-66781211-C-T is Benign according to our data. Variant chr15-66781211-C-T is described in ClinVar as [Benign]. Clinvar id is 413446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-66781211-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.083 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SMAD6	NM_005585.5 linkuse as main transcript	c.1167C>T	p.Phe389=	synonymous_variant	4/4	ENST00000288840.10	NP_005576.3
SMAD6	XM_011521561.3 linkuse as main transcript	c.384C>T	p.Phe128=	synonymous_variant	4/4		XP_011519863.1
SMAD6	NR_027654.2 linkuse as main transcript	n.2322C>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD6	ENST00000288840.10 linkuse as main transcript	c.1167C>T	p.Phe389=	synonymous_variant	4/4	1	NM_005585.5	ENSP00000288840	P1	O43541-1
SMAD6	ENST00000557916.5 linkuse as main transcript	c.*282C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000452955		O43541-4
SMAD6	ENST00000559931.5 linkuse as main transcript	c.*282C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	3		ENSP00000453446

Frequencies

GnomAD3 genomes

AF:

0.00789

AC:

1201

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.0244

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0160

AC:

3837

AN:

240116

Hom.:

279

AF XY:

0.0153

AC XY:

2020

AN XY:

131676

show subpopulations

Gnomad AFR exome

AF:

0.00247

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00272

Gnomad EAS exome

AF:

0.176

Gnomad SAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000248

Gnomad OTH exome

AF:

0.00927

GnomAD4 exome

AF:

0.00592

AC:

8627

AN:

1456052

Hom.:

531

Cov.:

AF XY:

0.00615

AC XY:

4456

AN XY:

724716

show subpopulations

Gnomad4 AFR exome

AF:

0.000897

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00395

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.0176

Gnomad4 FIN exome

AF:

0.0000415

Gnomad4 NFE exome

AF:

0.000214

Gnomad4 OTH exome

AF:

0.0151

GnomAD4 genome

AF:

0.00791

AC:

1205

AN:

152326

Hom.:

Cov.:

AF XY:

0.00866

AC XY:

645

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.171

Gnomad4 SAS

AF:

0.0244

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00846

Asia WGS

AF:

0.103

AC:

356

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 09, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jul 21, 2023

- -

Aortic valve disease 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.80

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