4-140525126-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153702.4(ELMOD2):c.-9-294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 216,048 control chromosomes in the GnomAD database, including 744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.086 (575 hom., cov: 33)
  • Exomes 𝑓: 0.071 (169 hom.)
• Consequence: ELMOD2 NM_153702.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73

Genes affected

ELMOD2 (HGNC:28111): (ELMO domain containing 2) This gene encodes one of six engulfment and motility (ELMO) domain-containing proteins. This gene is thought to play a role in antiviral responses. Mutations in this gene may be involved in the cause of familial idiopathic pulmonary fibrosis. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-140525126-A-G is Benign according to our data. Variant chr4-140525126-A-G is described in ClinVar as [Benign]. Clinvar id is 1280946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELMOD2	NM_153702.4	c.-9-294A>G		intron_variant		ENST00000323570.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELMOD2	ENST00000323570.8	c.-9-294A>G		intron_variant		1	NM_153702.4	P1

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13062 AN: 152190 Hom.: 576 Cov.: 33

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0702

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.0870

GnomAD4 exome AF: 0.0712 AC: 4536 AN: 63740 Hom.: 169 Cov.: 2 AF XY: 0.0716 AC XY: 2412 AN XY: 33704

Gnomad4 AFR exome AF: 0.0900

Gnomad4 AMR exome AF: 0.0925

Gnomad4 ASJ exome AF: 0.0888

Gnomad4 EAS exome AF: 0.0615

Gnomad4 SAS exome AF: 0.0873

Gnomad4 FIN exome AF: 0.0757

Gnomad4 NFE exome AF: 0.0667

Gnomad4 OTH exome AF: 0.0669

GnomAD4 genome AF: 0.0858 AC: 13074 AN: 152308 Hom.: 575 Cov.: 33 AF XY: 0.0874 AC XY: 6508 AN XY: 74482

Gnomad4 AFR AF: 0.0966

Gnomad4 AMR AF: 0.0978

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0699

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0852

Gnomad4 NFE AF: 0.0757

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0851 Hom.: 65

Bravo AF: 0.0869

Asia WGS AF: 0.0820 AC: 287 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.2
Dann	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs60943740; hg19: chr4-141446280;