chr4-140525544-T-G

Variant names:

• chr4-140525544-T-G
• rs150922490
• NM_153702.4:c.116T>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_153702.4(ELMOD2):​c.116T>G​(p.Val39Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,613,336 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (14 hom.)
• Consequence: ELMOD2 NM_153702.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.685
• Publications: 7 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005530894).
• BP6: Variant 4-140525544-T-G is Benign according to our data. Variant chr4-140525544-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 504726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 14 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.116T>G	p.Val39Gly	missense	Exon 2 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.116T>G	p.Val39Gly	missense	Exon 2 of 9	ENSP00000326342.3	Q8IZ81
	ELMOD2	ENST00000899909.1		c.116T>G	p.Val39Gly	missense	Exon 2 of 10	ENSP00000569968.1
	ELMOD2	ENST00000954139.1		c.116T>G	p.Val39Gly	missense	Exon 2 of 10	ENSP00000624198.1

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 346 AN: 152186 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00212 AC: 530 AN: 250376 AF XY: 0.00212

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.00181

Gnomad ASJ exome AF: 0.00835

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00310

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00299 AC: 4362 AN: 1461032 Hom.: 14 Cov.: 31 AF XY: 0.00297 AC XY: 2159 AN XY: 726772

African (AFR) AF: 0.000569 AC: 19 AN: 33410

American (AMR) AF: 0.00193 AC: 86 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.00785 AC: 205 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 86056

European-Finnish (FIN) AF: 0.000506 AC: 27 AN: 53410

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5760

European-Non Finnish (NFE) AF: 0.00343 AC: 3812 AN: 1111740

Other (OTH) AF: 0.00340 AC: 205 AN: 60360

GnomAD4 genome AF: 0.00227 AC: 346 AN: 152304 Hom.: 1 Cov.: 33 AF XY: 0.00218 AC XY: 162 AN XY: 74474

African (AFR) AF: 0.000794 AC: 33 AN: 41568

American (AMR) AF: 0.00510 AC: 78 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00316 AC: 215 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00365 Hom.: 2

Bravo AF: 0.00306

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00453 AC: 39

ExAC AF: 0.00191 AC: 232

EpiCase AF: 0.00442

EpiControl AF: 0.00374

ClinVar

ClinVar submissions

Significance: Likely 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	0.086
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.87
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.69
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.57	N
REVEL	Benign	0.11
Sift	Benign	0.36	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.21
MVP		0.16
MPC		0.049
ClinPred		0.0043	T
GERP RS		2.4
Varity_R		0.031
gMVP		0.47
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs150922490; hg19: chr4-141446698;