7-99119190-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181349.3(SMURF1):c.55+24536T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,810 control chromosomes in the GnomAD database, including 35,334 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 0.62 (35334 hom., cov: 29)
• Consequence: SMURF1 NM_181349.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMURF1	NM_181349.3	c.55+24536T>C		intron_variant		ENST00000361368.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMURF1	ENST00000361368.7	c.55+24536T>C		intron_variant		1	NM_181349.3	P1
SMURF1	ENST00000361125.1	c.55+24536T>C		intron_variant		1
SMURF1	ENST00000472627.1	n.477+1453T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94848 AN: 151694 Hom.: 35350 Cov.: 29

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.674

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.625 AC: 94829 AN: 151810 Hom.: 35334 Cov.: 29 AF XY: 0.630 AC XY: 46697 AN XY: 74170

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.670

Alfa AF: 0.655 Hom.: 7964

Bravo AF: 0.599

Asia WGS AF: 0.706 AC: 2456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.1
Dann	Benign	0.64

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: rs1128097; hg19: chr7-98716813;