rs111854052

Variant names:

• chr17-64604817-A-T
• rs111854052
• NM_022739.4:c.91+1785T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022739.4(SMURF2):​c.91+1785T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 151,978 control chromosomes in the GnomAD database, including 11 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 0.012 (11 hom., cov: 31)
• Consequence: SMURF2 NM_022739.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• Publications: 3 publications found

Genes affected

SMURF2 (HGNC:16809): (SMAD specific E3 ubiquitin protein ligase 2) Enables SMAD binding activity; identical protein binding activity; and ubiquitin-protein transferase activity. Involved in negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of trophoblast cell migration; and ubiquitin-dependent SMAD protein catabolic process. Located in nuclear speck. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0119 (1816/151978) while in subpopulation NFE AF = 0.0184 (1247/67950). AF 95% confidence interval is 0.0175. There are 11 homozygotes in GnomAd4. There are 873 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1816 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022739.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMURF2	NM_022739.4	MANE Select	c.91+1785T>A		intron	N/A	NP_073576.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMURF2	ENST00000262435.14	TSL:1 MANE Select	c.91+1785T>A		intron	N/A	ENSP00000262435.9
	SMURF2	ENST00000578386.5	TSL:1	n.91+1785T>A		intron	N/A	ENSP00000464432.1
	SMURF2	ENST00000585301.1	TSL:5	c.53-6327T>A		intron	N/A	ENSP00000463804.1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1816 AN: 151860 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.00310

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00312

Gnomad FIN AF: 0.00870

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0111

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

GnomAD4 genome AF: 0.0119 AC: 1816 AN: 151978 Hom.: 11 Cov.: 31 AF XY: 0.0117 AC XY: 873 AN XY: 74306

African (AFR) AF: 0.00309 AC: 128 AN: 41462

American (AMR) AF: 0.0159 AC: 243 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00312 AC: 15 AN: 4808

European-Finnish (FIN) AF: 0.00870 AC: 92 AN: 10572

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0184 AC: 1247 AN: 67950

Other (OTH) AF: 0.0109 AC: 23 AN: 2102

Alfa AF: 0.0133 Hom.: 3

Bravo AF: 0.0123

Asia WGS AF: 0.00231 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.2
DANN	Benign	0.60
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism

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: rs111854052; hg19: chr17-62600935;