7-36861974-T-G

Variant names:

• chr7-36861974-T-G
• rs7785934
• NM_014800.11:c.1906-238A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014800.11(ELMO1):​c.1906-238A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000026 in 384,310 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: ELMO1 NM_014800.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMO1	NM_014800.11	c.1906-238A>C		intron_variant	Intron 20 of 21	ENST00000310758.9	NP_055615.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMO1	ENST00000310758.9	c.1906-238A>C		intron_variant	Intron 20 of 21	1	NM_014800.11	ENSP00000312185.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000260 AC: 1 AN: 384310 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 202122

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11488

American (AMR) AF: 0.00 AC: 0 AN: 17754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11908

East Asian (EAS) AF: 0.00 AC: 0 AN: 28164

South Asian (SAS) AF: 0.00 AC: 0 AN: 37424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1760

European-Non Finnish (NFE) AF: 0.00000439 AC: 1 AN: 228016

Other (OTH) AF: 0.00 AC: 0 AN: 22424

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.65
PhyloP100		0.12

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: rs7785934; hg19: chr7-36901579;