Variant 7-99052428-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_181349.3(SMURF1):c.498C>G(p.Ser166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,579,302 control chromosomes in the GnomAD database, including 228,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.62 ( 31636 hom., cov: 33)

Exomes 𝑓: 0.52 ( 197192 hom. )

Consequence

SMURF1
NM_181349.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.18

Variant links:

Genes affected

SMURF1 (HGNC:16807): (SMAD specific E3 ubiquitin protein ligase 1) This gene encodes a ubiquitin ligase that is specific for receptor-regulated SMAD proteins in the bone morphogenetic protein (BMP) pathway. This protein plays a key roll in the regulation of cell motility, cell signalling, and cell polarity. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2010]

SMURF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 7-99052428-G-C is Benign according to our data. Variant chr7-99052428-G-C is described in ClinVar as [Benign]. Clinvar id is 1294535.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMURF1	NM_181349.3 linkuse as main transcript	c.498C>G	p.Ser166=	synonymous_variant	7/18	ENST00000361368.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMURF1	ENST00000361368.7 linkuse as main transcript	c.498C>G	p.Ser166=	synonymous_variant	7/18	1	NM_181349.3	P1	Q9HCE7-2
SMURF1	ENST00000361125.1 linkuse as main transcript	c.498C>G	p.Ser166=	synonymous_variant	7/19	1			Q9HCE7-1
SMURF1	ENST00000480055.5 linkuse as main transcript	n.796C>G		non_coding_transcript_exon_variant	7/7	3

Frequencies

GnomAD3 genomes

AF:

0.621

AC:

94417

AN:

151998

Hom.:

31575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.894

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.592

Gnomad EAS

AF:

0.643

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.609

GnomAD3 exomes

AF:

0.553

AC:

126546

AN:

228896

Hom.:

36224

AF XY:

0.548

AC XY:

67443

AN XY:

123176

show subpopulations

Gnomad AFR exome

AF:

0.908

Gnomad AMR exome

AF:

0.505

Gnomad ASJ exome

AF:

0.607

Gnomad EAS exome

AF:

0.637

Gnomad SAS exome

AF:

0.602

Gnomad FIN exome

AF:

0.444

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.537

GnomAD4 exome

AF:

0.520

AC:

742738

AN:

1427186

Hom.:

197192

Cov.:

AF XY:

0.522

AC XY:

368607

AN XY:

706220

show subpopulations

Gnomad4 AFR exome

AF:

0.915

Gnomad4 AMR exome

AF:

0.505

Gnomad4 ASJ exome

AF:

0.605

Gnomad4 EAS exome

AF:

0.634

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.444

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.544

GnomAD4 genome

AF:

0.621

AC:

94537

AN:

152116

Hom.:

31636

Cov.:

AF XY:

0.620

AC XY:

46077

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.894

Gnomad4 AMR

AF:

0.546

Gnomad4 ASJ

AF:

0.592

Gnomad4 EAS

AF:

0.642

Gnomad4 SAS

AF:

0.600

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.502

Gnomad4 OTH

AF:

0.613

Alfa

AF:

0.464

Hom.:

2411

Bravo

AF:

0.644

Asia WGS

AF:

0.643

AC:

2232

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.17

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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