Genetic Variant ELMOD2:c.399+4A>C (chr4-140537545-A-C) – 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.399+4A>C variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00222 in 1,597,698 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 56 hom. )

Consequence

ELMOD2
NM_153702.4 splice_region, intron

Scores

Splicing: ADA: 0.8539

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.98

Publications

3 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=-0.47).

BP6

Variant 4-140537545-A-C is Benign according to our data. Variant chr4-140537545-A-C is described in ClinVar as Benign. ClinVar VariationId is 504727.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00191 (290/152172) while in subpopulation EAS AF = 0.0279 (144/5162). AF 95% confidence interval is 0.0242. There are 6 homozygotes in GnomAd4. There are 185 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMOD2	NM_153702.4 link	c.399+4A>C		splice_region_variant, intron_variant	Intron 5 of 8	ENST00000323570.8	NP_714913.1	Q8IZ81

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ELMOD2	ENST00000323570.8 link	c.399+4A>C	splice_region_variant, intron_variant	Intron 5 of 8	1	NM_153702.4	ENSP00000326342.3	Q8IZ81
ELMOD2	ENST00000502397.5 link	c.399+4A>C	splice_region_variant, intron_variant	Intron 5 of 5	5		ENSP00000422582.1	D6RBS5
ELMOD2	ENST00000513606.1 link	c.168+4A>C	splice_region_variant, intron_variant	Intron 4 of 4	4		ENSP00000427592.1	D6RHX2
ELMOD2	ENST00000512057.1 link	n.544+4A>C	splice_region_variant, intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

291

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.0280

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00504

AC:

1193

AN:

236620

AF XY:

0.00559

show subpopulations

Gnomad AFR exome

AF:

0.000331

Gnomad AMR exome

AF:

0.0000978

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.0286

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.000393

Gnomad OTH exome

AF:

0.00352

GnomAD4 exome

AF:

0.00225

AC:

3249

AN:

1445526

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

1963

AN XY:

718312

show subpopulations

African (AFR)

AF:

0.0000928

AC:

AN:

32330

American (AMR)

AF:

0.0000952

AC:

AN:

42010

Ashkenazi Jewish (ASJ)

AF:

0.00421

AC:

109

AN:

25884

East Asian (EAS)

AF:

0.0251

AC:

969

AN:

38536

South Asian (SAS)

AF:

0.0216

AC:

1769

AN:

81960

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

53064

Middle Eastern (MID)

AF:

0.000872

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.000138

AC:

153

AN:

1106206

Other (OTH)

AF:

0.00388

AC:

232

AN:

59800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

147

294

442

589

736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.00191

AC:

290

AN:

152172

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

185

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41552

American (AMR)

AF:

0.0000655

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3470

East Asian (EAS)

AF:

0.0279

AC:

144

AN:

5162

South Asian (SAS)

AF:

0.0205

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000324

AC:

AN:

67992

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.000762

Hom.:

Bravo

AF:

0.00174

Asia WGS

AF:

0.0300

AC:

109

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

399+4A>C in intron 5 of ELMOD2: This variant is not expected to have clinical si gnificance because it has been identified in 3.5% (7/200) of Han Chinese chromos omes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.ni h.gov/projects/SNP; dbSNP rs149594258). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

4.0

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.85

dbscSNV1_RF

Benign

0.54

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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