rs148286208

Variant names:

• chr4-140543512-G-A
• rs148286208
• NM_153702.4:c.662G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-140543512-G-A
• chr4-140543512-G-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_153702.4(ELMOD2):​c.662G>A​(p.Ser221Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000913 in 1,606,730 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S221T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (2 hom.)
• Consequence: ELMOD2 NM_153702.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.96
• Publications: 3 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005897492).
• BP6: Variant 4-140543512-G-A is Benign according to our data. Variant chr4-140543512-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3044639.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.662G>A	p.Ser221Asn	missense	Exon 8 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.662G>A	p.Ser221Asn	missense	Exon 8 of 9	ENSP00000326342.3	Q8IZ81
	ELMOD2	ENST00000899909.1		c.707G>A	p.Ser236Asn	missense	Exon 9 of 10	ENSP00000569968.1
	ELMOD2	ENST00000954139.1		c.707G>A	p.Ser236Asn	missense	Exon 9 of 10	ENSP00000624198.1

Frequencies

GnomAD3 genomes AF: 0.000750 AC: 114 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000993 AC: 243 AN: 244610 AF XY: 0.00109

Gnomad AFR exome AF: 0.000188

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00205

Gnomad NFE exome AF: 0.00173

Gnomad OTH exome AF: 0.000336

GnomAD4 exome AF: 0.000930 AC: 1353 AN: 1454532 Hom.: 2 Cov.: 30 AF XY: 0.000965 AC XY: 698 AN XY: 723664

African (AFR) AF: 0.0000604 AC: 2 AN: 33096

American (AMR) AF: 0.0000234 AC: 1 AN: 42666

Ashkenazi Jewish (ASJ) AF: 0.000154 AC: 4 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39304

South Asian (SAS) AF: 0.00 AC: 0 AN: 84772

European-Finnish (FIN) AF: 0.00241 AC: 128 AN: 53178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00107 AC: 1182 AN: 1109768

Other (OTH) AF: 0.000599 AC: 36 AN: 60064

GnomAD4 genome AF: 0.000749 AC: 114 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000712 AC XY: 53 AN XY: 74418

African (AFR) AF: 0.000168 AC: 7 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00115 AC: 78 AN: 67940

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000903 Hom.: 0

Bravo AF: 0.000518

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.00123 AC: 149

Asia WGS AF: 0.000289 AC: 1 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ELMOD2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.073
Sift	Benign	0.15	T
Sift4G	Benign	0.13	T
Polyphen		0.020	B
Vest4		0.15
MVP		0.14
MPC		0.041
ClinPred		0.040	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.43
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148286208; hg19: chr4-141464666; COSMIC: COSV106100628; COSMIC: COSV106100628;