7-99119190-A-G

Variant names:

• chr7-99119190-A-G
• rs1128097
• NM_181349.3:c.55+24536T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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.

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.55+24536T>C		intron	N/A	NP_851994.1	Q9HCE7-2
	SMURF1	NM_020429.3		c.55+24536T>C		intron	N/A	NP_065162.1	Q9HCE7-1
	SMURF1	NM_001199847.2		c.55+24536T>C		intron	N/A	NP_001186776.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMURF1	ENST00000361368.7	TSL:1 MANE Select	c.55+24536T>C		intron	N/A	ENSP00000355326.2	Q9HCE7-2
	SMURF1	ENST00000361125.1	TSL:1	c.55+24536T>C		intron	N/A	ENSP00000354621.1	Q9HCE7-1
	SMURF1	ENST00000885289.1		c.55+24536T>C		intron	N/A	ENSP00000555348.1

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

African (AFR) AF: 0.188 AC: 7790 AN: 41392

American (AMR) AF: 0.731 AC: 11130 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2600 AN: 3470

East Asian (EAS) AF: 0.872 AC: 4510 AN: 5170

South Asian (SAS) AF: 0.687 AC: 3299 AN: 4800

European-Finnish (FIN) AF: 0.853 AC: 8980 AN: 10526

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54213 AN: 67916

Other (OTH) AF: 0.670 AC: 1404 AN: 2096

Alfa AF: 0.684 Hom.: 14880

Bravo AF: 0.599

Asia WGS AF: 0.706 AC: 2456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.64
PhyloP100		0.42
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs1128097; hg19: chr7-98716813;