Variant chr7-99052428-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_181349.3(SMURF1):c.498C>A(p.Ser166Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000495 in 1,580,132 control chromosomes in the GnomAD database, including 5 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 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 4 hom. )

Consequence

SMURF1
NM_181349.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

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

BS2

High AC in GnomAd4 at 375 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMURF1	NM_181349.3 link	c.498C>A	p.Ser166Ser	synonymous_variant	7/18	ENST00000361368.7	NP_851994.1	Q9HCE7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMURF1	ENST00000361368.7 link	c.498C>A	p.Ser166Ser	synonymous_variant	7/18	1	NM_181349.3	ENSP00000355326.2	Q9HCE7-2
SMURF1	ENST00000361125.1 link	c.498C>A	p.Ser166Ser	synonymous_variant	7/19	1		ENSP00000354621.1	Q9HCE7-1
SMURF1	ENST00000480055.5 link	n.796C>A		non_coding_transcript_exon_variant	7/7	3

Frequencies

GnomAD3 genomes

AF:

0.00247

AC:

376

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000773

AC:

177

AN:

228896

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

123176

show subpopulations

Gnomad AFR exome

AF:

0.00948

Gnomad AMR exome

AF:

0.000565

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000563

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000380

Gnomad OTH exome

AF:

0.000733

GnomAD4 exome

AF:

0.000285

AC:

407

AN:

1427980

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

160

AN XY:

706672

show subpopulations

Gnomad4 AFR exome

AF:

0.00784

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000622

Gnomad4 OTH exome

AF:

0.000577

GnomAD4 genome

AF:

0.00246

AC:

375

AN:

152152

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00859

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000517

Hom.:

2411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.17

DANN

Benign

0.57

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over