rs142450830

Positions:

• chr4-140540196-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000323570.8(ELMOD2):​c.428A>C​(p.Lys143Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00182 in 1,614,188 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (27 hom.)
• Consequence: ELMOD2 ENST00000323570.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.84

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062583685).
• BP6: Variant 4-140540196-A-C is Benign according to our data. Variant chr4-140540196-A-C is described in ClinVar as [Benign]. Clinvar id is 226630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0032 (488/152340) while in subpopulation EAS AF= 0.0202 (105/5192). AF 95% confidence interval is 0.0171. There are 6 homozygotes in gnomad4. There are 334 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD2	NM_153702.4	c.428A>C	p.Lys143Thr	missense_variant	6/9	ENST00000323570.8	NP_714913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMOD2	ENST00000323570.8	c.428A>C	p.Lys143Thr	missense_variant	6/9	1	NM_153702.4	ENSP00000326342	P1
ELMOD2	ENST00000502397.5	c.428A>C	p.Lys143Thr	missense_variant	6/6	5		ENSP00000422582
ELMOD2	ENST00000513606.1	c.197A>C	p.Lys66Thr	missense_variant	5/5	4		ENSP00000427592
ELMOD2	ENST00000512057.1	n.573A>C		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes AF: 0.00321 AC: 489 AN: 152222 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0307

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00435 AC: 1094 AN: 251426 Hom.: 17 AF XY: 0.00398 AC XY: 541 AN XY: 135888

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0210

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.0278

Gnomad NFE exome AF: 0.000633

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00168 AC: 2457 AN: 1461848 Hom.: 27 Cov.: 30 AF XY: 0.00161 AC XY: 1168 AN XY: 727224

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0187

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0260

Gnomad4 NFE exome AF: 0.000156

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00320 AC: 488 AN: 152340 Hom.: 6 Cov.: 32 AF XY: 0.00448 AC XY: 334 AN XY: 74494

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0202

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0307

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00122 Hom.: 3

Bravo AF: 0.00107

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00404 AC: 490

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Lys143Thr in exon 6 of ELMOD2: This variant is not expected to have clinical sig nificance because it has been identified in 3.6% (7/194) of Han Chinese chromoso mes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih .gov/projects/SNP; dbSNP rs142450830). -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.10
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T;T;T
MetaRNN	Benign	0.0063	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.099
Sift	Benign	0.042	D;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.22
MVP		0.16
MPC		0.050
ClinPred		0.035	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs142450830; hg19: chr4-141461350;