Genetic Variant ELMOD2:c.*9C>T (chr4-140550384-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_153702.4(ELMOD2):c.*9C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,585,338 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 25 hom. )

Consequence

ELMOD2
NM_153702.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0870

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-140550384-C-T is Benign according to our data. Variant chr4-140550384-C-T is described in ClinVar as Benign. ClinVar VariationId is 226629.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00137 (1961/1433032) while in subpopulation AMR AF = 0.0259 (999/38644). AF 95% confidence interval is 0.0245. There are 25 homozygotes in GnomAdExome4. There are 880 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ELMOD2	NM_153702.4 link	c.*9C>T	3_prime_UTR_variant	Exon 9 of 9	ENST00000323570.8	NP_714913.1
ELMOD2	XM_005262885.4 link	c.*9C>T	3_prime_UTR_variant	Exon 9 of 9		XP_005262942.1
ELMOD2	XM_011531819.3 link	c.*9C>T	3_prime_UTR_variant	Exon 9 of 9		XP_011530121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMOD2	ENST00000323570.8 link	c.*9C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_153702.4	ENSP00000326342.3
ELMOD2	ENST00000502290.1 link	n.507C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00226

AC:

344

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00566

AC:

1299

AN:

229676

AF XY:

0.00452

show subpopulations

Gnomad AFR exome

AF:

0.000922

Gnomad AMR exome

AF:

0.0311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0150

Gnomad FIN exome

AF:

0.00211

Gnomad NFE exome

AF:

0.000584

Gnomad OTH exome

AF:

0.00289

GnomAD4 exome

AF:

0.00137

AC:

1961

AN:

1433032

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

880

AN XY:

711762

show subpopulations

African (AFR)

AF:

0.000438

AC:

AN:

31966

American (AMR)

AF:

0.0259

AC:

999

AN:

38644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25144

East Asian (EAS)

AF:

0.0118

AC:

462

AN:

39010

South Asian (SAS)

AF:

0.00102

AC:

AN:

81148

European-Finnish (FIN)

AF:

0.00208

AC:

109

AN:

52368

Middle Eastern (MID)

AF:

0.000438

AC:

AN:

4566

European-Non Finnish (NFE)

AF:

0.000189

AC:

208

AN:

1101060

Other (OTH)

AF:

0.00142

AC:

AN:

59126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

164

245

327

409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00225

AC:

343

AN:

152306

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41580

American (AMR)

AF:

0.0123

AC:

188

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0135

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68024

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00371

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 12, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

*9C>T in exon 9 of ELMOD2: This variant is not expected to have clinical signifi cance because it has been identified in 3.0% (359/11216), including 5 homozygote s of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs75824346). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.9

(source)

DANN

Benign

0.57

PhyloP100

-0.087

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over