rs6964474

Variant names:

• chr7-37398993-T-G
• rs6964474
• NM_014800.11:c.-74+49682A>C

Variant summary

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

The NM_014800.11(ELMO1):​c.-74+49682A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,058 control chromosomes in the GnomAD database, including 10,290 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 0.33 (10290 hom., cov: 32)
• Consequence: ELMO1 NM_014800.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMO1	NM_014800.11	c.-74+49682A>C		intron_variant	Intron 1 of 21	ENST00000310758.9	NP_055615.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMO1	ENST00000310758.9	c.-74+49682A>C		intron_variant	Intron 1 of 21	1	NM_014800.11	ENSP00000312185.4

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50621 AN: 151940 Hom.: 10273 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.333 AC: 50679 AN: 152058 Hom.: 10290 Cov.: 32 AF XY: 0.333 AC XY: 24729 AN XY: 74340

African (AFR) AF: 0.568 AC: 23541 AN: 41436

American (AMR) AF: 0.276 AC: 4219 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2094 AN: 5152

South Asian (SAS) AF: 0.331 AC: 1598 AN: 4826

European-Finnish (FIN) AF: 0.218 AC: 2308 AN: 10600

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15075 AN: 67980

Other (OTH) AF: 0.314 AC: 661 AN: 2106

Alfa AF: 0.253 Hom.: 9487

Bravo AF: 0.348

Asia WGS AF: 0.370 AC: 1285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.75
PhyloP100		-0.25
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: rs6964474; hg19: chr7-37438596;