rs10488029

Variant names:

• chr7-37027790-A-G
• rs10488029
• NM_014800.11:c.1301-14355T>C

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_014800.11(ELMO1):c.1301-14355T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.137 (AC=20,819) in the gnomAD database across 151,876 control chromosomes, including 1,728 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.223. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1728 hom., cov: 31)
• Consequence: ELMO1 NM_014800.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 8 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

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.2231 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_014800.11. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMO1	NM_014800.11	MANE Select	c.1301-14355T>C		intron	N/A	NP_055615.8
	ELMO1	NM_001206480.2		c.1301-14355T>C		intron	N/A	NP_001193409.1	A4D1X5
	ELMO1	NM_001206482.2		c.1301-14355T>C		intron	N/A	NP_001193411.1	Q92556-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMO1	ENST00000310758.9	TSL:1 MANE Select	c.1301-14355T>C		intron	N/A	ENSP00000312185.4	Q92556-1
	ELMO1	ENST00000448602.5	TSL:1	c.1301-14355T>C		intron	N/A	ENSP00000394458.1	Q92556-1
	ELMO1	ENST00000442504.5	TSL:2	c.1301-14355T>C		intron	N/A	ENSP00000406952.1	Q92556-1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.137	AC:20809	Hom:1729	AN:151760	Cov:31
GnomAD4 genome	AF: 0.137	AC:20819	Hom:1728	AN:151876	Cov:31
TOPMed (Bravo)	AF: 0.150	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.127	AC:16764	Hom:1389	AN:132032	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.162	AC:380	Hom:30	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.0780	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.0433	AC:13	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.0940	AC:328	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.0690	AC:498	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.171	AC:30	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0388	AC:4748	Hom:108	AN:122324	Cov:
Turkish Variome	AF: 0.153	AC:237	Hom:26	AN:1546	Cov:
UK10K	AF: 0.0894	AC:676	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.0778	AC:697	Hom:30	AN:8960	Cov:

Showing 14 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.7
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.39
GPN-Star LLR	N/A	0.65
GPN-Star score	N/A	-0.65
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.25

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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: rs10488029;

hg19: chr7-37067395;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar