NM_153702.4:c.428A>C

Variant names:

• chr4-140540196-A-C
• rs142450830
• NM_153702.4:c.428A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_153702.4(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 NM_153702.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.84
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153702.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMOD2	NM_153702.4	MANE Select	c.428A>C	p.Lys143Thr	missense	Exon 6 of 9	NP_714913.1	Q8IZ81

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMOD2	ENST00000323570.8	TSL:1 MANE Select	c.428A>C	p.Lys143Thr	missense	Exon 6 of 9	ENSP00000326342.3	Q8IZ81
	ELMOD2	ENST00000899909.1		c.473A>C	p.Lys158Thr	missense	Exon 7 of 10	ENSP00000569968.1
	ELMOD2	ENST00000954139.1		c.473A>C	p.Lys158Thr	missense	Exon 7 of 10	ENSP00000624198.1

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

GnomAD2 exomes AF: 0.00435 AC: 1094 AN: 251426 AF XY: 0.00398

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 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

African (AFR) AF: 0.000119 AC: 4 AN: 33478

American (AMR) AF: 0.000157 AC: 7 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0187 AC: 741 AN: 39686

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86256

European-Finnish (FIN) AF: 0.0260 AC: 1389 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000156 AC: 174 AN: 1111996

Other (OTH) AF: 0.00219 AC: 132 AN: 60392

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

African (AFR) AF: 0.000120 AC: 5 AN: 41590

American (AMR) AF: 0.000392 AC: 6 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0202 AC: 105 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0307 AC: 326 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68022

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00135 Hom.: 4

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.10
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.8
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.099
Sift	Benign	0.042	D
Sift4G	Benign	0.15	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
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs142450830; hg19: chr4-141461350;