rs1033475

Variant names:

• chr20-46417289-A-C
• rs1033475
• ENST00000400371.2:n.1986-2325T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000400371.2(ENSG00000293461):​n.1986-2325T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 152,306 control chromosomes in the GnomAD database, including 240 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 0.033 (240 hom., cov: 32)
• Consequence: ENSG00000293461 ENST00000400371.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774
• Publications: 2 publications found

Genes affected

ENSG00000293461 (HGNC:):

ELMO2 (HGNC:17233): (engulfment and cell motility 2) The protein encoded by this gene interacts with the dedicator of cyto-kinesis 1 protein. Similarity to a C. elegans protein suggests that this protein may function in phagocytosis of apoptotic cells and in cell migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ELMO2 Gene-Disease associations (from GenCC):

• primary intraosseous venous malformation

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• Ramon syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000400371.2. 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
	LOC105372633	NR_146919.1		n.71-5866A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000293461	ENST00000400371.2	TSL:1	n.1986-2325T>G		intron	N/A
	ELMO2	ENST00000487583.5	TSL:5	n.92+15605T>G		intron	N/A
	ENSG00000293461	ENST00000849666.1		n.358-2325T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5016 AN: 152188 Hom.: 239 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0292

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

GnomAD4 genome AF: 0.0330 AC: 5026 AN: 152306 Hom.: 240 Cov.: 32 AF XY: 0.0312 AC XY: 2322 AN XY: 74478

African (AFR) AF: 0.110 AC: 4565 AN: 41530

American (AMR) AF: 0.0197 AC: 301 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 68040

Other (OTH) AF: 0.0289 AC: 61 AN: 2112

Alfa AF: 0.0244 Hom.: 25

Bravo AF: 0.0372

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.9
DANN	Benign	0.64
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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: rs1033475;

hg19: chr20-45045928;