rs4723593

Variant names:

• chr7-36907687-G-A
• rs4723593
• NM_014800.11:c.1438-12670C>T

Variant summary

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

The NM_014800.11(ELMO1):​c.1438-12670C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,140 control chromosomes in the GnomAD database, including 1,758 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 0.14 (1758 hom., cov: 32)
• Consequence: ELMO1 NM_014800.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 4 publications found

Genes affected

ELMO1 (HGNC:16286): (engulfment and cell motility 1) This gene encodes a member of the engulfment and cell motility protein family. These proteins interact with dedicator of cytokinesis proteins to promote phagocytosis and cell migration. Increased expression of this gene and dedicator of cytokinesis 1 may promote glioma cell invasion, and single nucleotide polymorphisms in this gene may be associated with diabetic nephropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ELMO1 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014800.11. 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
	ELMO1	NM_014800.11	MANE Select	c.1438-12670C>T		intron	N/A	NP_055615.8
	ELMO1	NM_001206480.2		c.1438-12670C>T		intron	N/A	NP_001193409.1
	ELMO1	NM_001206482.2		c.1438-12670C>T		intron	N/A	NP_001193411.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMO1	ENST00000310758.9	TSL:1 MANE Select	c.1438-12670C>T		intron	N/A	ENSP00000312185.4
	ELMO1	ENST00000448602.5	TSL:1	c.1438-12670C>T		intron	N/A	ENSP00000394458.1
	ELMO1	ENST00000396040.6	TSL:1	c.-3-12670C>T		intron	N/A	ENSP00000379355.2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21932 AN: 152022 Hom.: 1750 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.144 AC: 21966 AN: 152140 Hom.: 1758 Cov.: 32 AF XY: 0.149 AC XY: 11080 AN XY: 74370

African (AFR) AF: 0.0881 AC: 3654 AN: 41496

American (AMR) AF: 0.206 AC: 3146 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 602 AN: 3468

East Asian (EAS) AF: 0.158 AC: 816 AN: 5164

South Asian (SAS) AF: 0.224 AC: 1078 AN: 4818

European-Finnish (FIN) AF: 0.201 AC: 2129 AN: 10582

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10056 AN: 68002

Other (OTH) AF: 0.162 AC: 342 AN: 2116

Alfa AF: 0.148 Hom.: 226

Bravo AF: 0.139

Asia WGS AF: 0.197 AC: 685 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.38
PhyloP100		-0.069
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: rs4723593; hg19: chr7-36947292;