rs6974491

Variant names:

• chr7-37334906-G-A
• rs6974491
• NM_014800.11:c.78+7707C>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.78+7707C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,104 control chromosomes in the GnomAD database, including 1,492 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 0.13 (1492 hom., cov: 32)
• Consequence: ELMO1 NM_014800.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 43 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMO1	NM_014800.11	c.78+7707C>T		intron_variant	Intron 2 of 21	ENST00000310758.9	NP_055615.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMO1	ENST00000310758.9	c.78+7707C>T		intron_variant	Intron 2 of 21	1	NM_014800.11	ENSP00000312185.4

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20352 AN: 151984 Hom.: 1493 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.134 AC: 20365 AN: 152104 Hom.: 1492 Cov.: 32 AF XY: 0.131 AC XY: 9752 AN XY: 74354

African (AFR) AF: 0.0876 AC: 3634 AN: 41480

American (AMR) AF: 0.156 AC: 2385 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3472

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5178

South Asian (SAS) AF: 0.112 AC: 543 AN: 4828

European-Finnish (FIN) AF: 0.127 AC: 1340 AN: 10554

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11646 AN: 67988

Other (OTH) AF: 0.142 AC: 300 AN: 2110

Alfa AF: 0.156 Hom.: 8602

Bravo AF: 0.133

Asia WGS AF: 0.0590 AC: 207 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.15
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: rs6974491; hg19: chr7-37374510; COSMIC: COSV60322294;