Genetic Variant ELMOD2:c.270-81T>G (chr4-140537331-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153702.4(ELMOD2):c.270-81T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,224,476 control chromosomes in the GnomAD database, including 270,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 25445 hom., cov: 31)

Exomes 𝑓: 0.67 ( 245262 hom. )

Consequence

ELMOD2
NM_153702.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.217

Variant links:

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]

ELMOD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 4-140537331-T-G is Benign according to our data. Variant chr4-140537331-T-G is described in ClinVar as [Benign]. Clinvar id is 1235399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMOD2	NM_153702.4 link	c.270-81T>G		intron_variant	Intron 4 of 8	ENST00000323570.8	NP_714913.1	Q8IZ81

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ELMOD2	ENST00000323570.8 link	c.270-81T>G	intron_variant	Intron 4 of 8	1	NM_153702.4	ENSP00000326342.3	Q8IZ81
ELMOD2	ENST00000502397.5 link	c.270-81T>G	intron_variant	Intron 4 of 5	5		ENSP00000422582.1	D6RBS5
ELMOD2	ENST00000513606.1 link	c.39-81T>G	intron_variant	Intron 3 of 4	4		ENSP00000427592.1	D6RHX2
ELMOD2	ENST00000512057.1 link	n.415-81T>G	intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84416

AN:

151852

Hom.:

25440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.631

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.661

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.690

Gnomad OTH

AF:

0.574

GnomAD4 exome

AF:

0.671

AC:

719894

AN:

1072506

Hom.:

245262

AF XY:

0.669

AC XY:

352333

AN XY:

526828

show subpopulations

Gnomad4 AFR exome

AF:

0.295

Gnomad4 AMR exome

AF:

0.562

Gnomad4 ASJ exome

AF:

0.643

Gnomad4 EAS exome

AF:

0.539

Gnomad4 SAS exome

AF:

0.528

Gnomad4 FIN exome

AF:

0.670

Gnomad4 NFE exome

AF:

0.696

Gnomad4 OTH exome

AF:

0.641

GnomAD4 genome

AF:

0.556

AC:

84453

AN:

151970

Hom.:

25445

Cov.:

AF XY:

0.552

AC XY:

40994

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.309

Gnomad4 AMR

AF:

0.560

Gnomad4 ASJ

AF:

0.631

Gnomad4 EAS

AF:

0.492

Gnomad4 SAS

AF:

0.514

Gnomad4 FIN

AF:

0.661

Gnomad4 NFE

AF:

0.690

Gnomad4 OTH

AF:

0.574

Alfa

AF:

0.602

Hom.:

4297

Bravo

AF:

0.538

Asia WGS

AF:

0.481

AC:

1669

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over