rs219825

Positions:

• chr7-99047942-C-G

Variant summary

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

The NM_181349.3(SMURF1):​c.954-60G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,525,540 control chromosomes in the GnomAD database, including 120,878 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 0.47 (18841 hom., cov: 33)
  • Exomes 𝑓: 0.38 (102037 hom.)
• Consequence: SMURF1 NM_181349.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484

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]

TRRAP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMURF1	NM_181349.3	c.954-60G>C		intron_variant		ENST00000361368.7	NP_851994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMURF1	ENST00000361368.7	c.954-60G>C		intron_variant		1	NM_181349.3	ENSP00000355326.2
SMURF1	ENST00000361125.1	c.1032-60G>C		intron_variant		1		ENSP00000354621.1
TRRAP	ENST00000468960.3	n.1009C>G		non_coding_transcript_exon_variant	5/5	4
TRRAP	ENST00000482799.3	n.1092C>G		non_coding_transcript_exon_variant	6/6	3

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70889 AN: 152040 Hom.: 18803 Cov.: 33

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.381 AC: 523085 AN: 1373382 Hom.: 102037 Cov.: 22 AF XY: 0.381 AC XY: 262246 AN XY: 687454

Gnomad4 AFR exome AF: 0.765

Gnomad4 AMR exome AF: 0.332

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.455

Gnomad4 FIN exome AF: 0.329

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.467 AC: 70989 AN: 152158 Hom.: 18841 Cov.: 33 AF XY: 0.463 AC XY: 34449 AN XY: 74372

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.471

Alfa AF: 0.413 Hom.: 1803

Bravo AF: 0.482

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.8
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs219825; hg19: chr7-98645565; COSMIC: COSV63155762; COSMIC: COSV63155762;