rs219797

Variant names:

• chr7-99052428-G-C
• rs219797
• NM_181349.3:c.498C>G
• SMURF1 p.Ser166Ser

Your query was ambiguous. Multiple possible variants found:

• chr7-99052428-G-C
• chr7-99052428-G-A
• chr7-99052428-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_181349.3(SMURF1):​c.498C>G​(p.Ser166Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.18
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -21 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 VariationId is 1294535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181349.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMURF1	NM_181349.3	MANE Select	c.498C>G	p.Ser166Ser	synonymous	Exon 7 of 18	NP_851994.1	Q9HCE7-2
	SMURF1	NM_020429.3		c.498C>G	p.Ser166Ser	synonymous	Exon 7 of 19	NP_065162.1	Q9HCE7-1
	SMURF1	NM_001199847.2		c.498C>G	p.Ser166Ser	synonymous	Exon 7 of 18	NP_001186776.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMURF1	ENST00000361368.7	TSL:1 MANE Select	c.498C>G	p.Ser166Ser	synonymous	Exon 7 of 18	ENSP00000355326.2	Q9HCE7-2
	SMURF1	ENST00000361125.1	TSL:1	c.498C>G	p.Ser166Ser	synonymous	Exon 7 of 19	ENSP00000354621.1	Q9HCE7-1
	SMURF1	ENST00000885289.1		c.498C>G	p.Ser166Ser	synonymous	Exon 7 of 19	ENSP00000555348.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94417 AN: 151998 Hom.: 31575 Cov.: 33

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

GnomAD2 exomes AF: 0.553 AC: 126546 AN: 228896 AF XY: 0.548

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 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.: 49 AF XY: 0.522 AC XY: 368607 AN XY: 706220

African (AFR) AF: 0.915 AC: 29869 AN: 32658

American (AMR) AF: 0.505 AC: 20701 AN: 40962

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 14688 AN: 24278

East Asian (EAS) AF: 0.634 AC: 24774 AN: 39082

South Asian (SAS) AF: 0.591 AC: 47201 AN: 79826

European-Finnish (FIN) AF: 0.444 AC: 23344 AN: 52578

Middle Eastern (MID) AF: 0.606 AC: 3408 AN: 5628

European-Non Finnish (NFE) AF: 0.500 AC: 546665 AN: 1093232

Other (OTH) AF: 0.544 AC: 32088 AN: 58942

GnomAD4 genome AF: 0.621 AC: 94537 AN: 152116 Hom.: 31636 Cov.: 33 AF XY: 0.620 AC XY: 46077 AN XY: 74356

African (AFR) AF: 0.894 AC: 37138 AN: 41532

American (AMR) AF: 0.546 AC: 8354 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2054 AN: 3468

East Asian (EAS) AF: 0.642 AC: 3304 AN: 5144

South Asian (SAS) AF: 0.600 AC: 2895 AN: 4826

European-Finnish (FIN) AF: 0.457 AC: 4820 AN: 10558

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34091 AN: 67976

Other (OTH) AF: 0.613 AC: 1294 AN: 2112

Alfa AF: 0.464 Hom.: 2411

Bravo AF: 0.644

Asia WGS AF: 0.643 AC: 2232 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.17
DANN	Benign	0.65
PhyloP100		-6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs219797;

hg19: chr7-98650051;

COSMIC: COSV63157525;

COSMIC: COSV63157525;