rs647756

Variant names:

• chr11-107665032-G-A
• rs647756
• NM_018712.4:c.840G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ELMOD1	NM_018712.4	c.840G>A	p.Leu280Leu	synonymous_variant	Exon 12 of 12	ENST00000265840.12	NP_061182.3
ELMOD1	NM_001308018.2	c.822G>A	p.Leu274Leu	synonymous_variant	Exon 13 of 13		NP_001294947.1
ELMOD1	NM_001130037.2	c.816G>A	p.Leu272Leu	synonymous_variant	Exon 11 of 11		NP_001123509.1

Ensembl

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

GnomAD2 exomes AF: 0.132 AC: 32845 AN: 248212 AF XY: 0.120

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 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

African (AFR) AF: 0.609 AC: 20346 AN: 33386

American (AMR) AF: 0.173 AC: 7701 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.0874 AC: 2280 AN: 26074

East Asian (EAS) AF: 0.357 AC: 14171 AN: 39650

South Asian (SAS) AF: 0.0982 AC: 8442 AN: 85964

European-Finnish (FIN) AF: 0.0601 AC: 3205 AN: 53362

Middle Eastern (MID) AF: 0.0891 AC: 514 AN: 5766

European-Non Finnish (NFE) AF: 0.0531 AC: 58931 AN: 1110674

Other (OTH) AF: 0.113 AC: 6806 AN: 60288

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

African (AFR) AF: 0.577 AC: 23854 AN: 41320

American (AMR) AF: 0.198 AC: 3027 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 307 AN: 3468

East Asian (EAS) AF: 0.326 AC: 1676 AN: 5148

South Asian (SAS) AF: 0.111 AC: 535 AN: 4812

European-Finnish (FIN) AF: 0.0674 AC: 709 AN: 10526

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0590 AC: 4007 AN: 67960

Other (OTH) AF: 0.183 AC: 387 AN: 2112

Alfa AF: 0.121 Hom.: 9682

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
PhyloP100		7.4
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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