rs647756

Positions:

• chr11-107665032-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_018712.4(ELMOD1):​c.840G>A​(p.Leu280Leu) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 1,611,566 control chromosomes in the GnomAD database, including 20,405 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 0.23 (7789 hom., cov: 31)
  • Exomes 𝑓: 0.084 (12616 hom.)
• Consequence: ELMOD1 NM_018712.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.41

Genes affected

ELMOD1 (HGNC:25334): (ELMO domain containing 1) Enables GTPase activator activity. Predicted to be involved in positive regulation of GTPase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD1	NM_018712.4	c.840G>A	p.Leu280Leu	synonymous_variant	12/12	ENST00000265840.12	NP_061182.3
ELMOD1	NM_001308018.2	c.822G>A	p.Leu274Leu	synonymous_variant	13/13		NP_001294947.1
ELMOD1	NM_001130037.2	c.816G>A	p.Leu272Leu	synonymous_variant	11/11		NP_001123509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMOD1	ENST00000265840.12	c.840G>A	p.Leu280Leu	synonymous_variant	12/12	1	NM_018712.4	ENSP00000265840.7
ELMOD1	ENST00000531234.5	c.822G>A	p.Leu274Leu	synonymous_variant	13/13	2		ENSP00000433232.1
ELMOD1	ENST00000443271.2	c.816G>A	p.Leu272Leu	synonymous_variant	11/11	2		ENSP00000412257.2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34451 AN: 151702 Hom.: 7758 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.132 AC: 32845 AN: 248212 Hom.: 4701 AF XY: 0.120 AC XY: 16185 AN XY: 134642

Gnomad AFR exome AF: 0.596

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.0861

Gnomad EAS exome AF: 0.311

Gnomad SAS exome AF: 0.0971

Gnomad FIN exome AF: 0.0643

Gnomad NFE exome AF: 0.0566

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.0838 AC: 122396 AN: 1459746 Hom.: 12616 Cov.: 31 AF XY: 0.0826 AC XY: 59950 AN XY: 726120

Gnomad4 AFR exome AF: 0.609

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.0874

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.0982

Gnomad4 FIN exome AF: 0.0601

Gnomad4 NFE exome AF: 0.0531

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.227 AC: 34532 AN: 151820 Hom.: 7789 Cov.: 31 AF XY: 0.226 AC XY: 16793 AN XY: 74206

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0674

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.183

Alfa AF: 0.0910 Hom.: 3308

Bravo AF: 0.252

Asia WGS AF: 0.222 AC: 771 AN: 3478

EpiCase AF: 0.0546

EpiControl AF: 0.0536

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs647756; hg19: chr11-107535758; COSMIC: COSV56191221;