rs149594258

chr4-140537545-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_153702.4(ELMOD2):c.399+4A>C variant causes a splice donor 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. 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_donor_region, intron
• Scores: Splicing: ADA: 0.8539
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.98

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 -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELMOD2	NM_153702.4	c.399+4A>C		splice_donor_region_variant, intron_variant		ENST00000323570.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELMOD2	ENST00000323570.8	c.399+4A>C		splice_donor_region_variant, intron_variant		1	NM_153702.4	P1
ELMOD2	ENST00000502397.5	c.399+4A>C		splice_donor_region_variant, intron_variant		5
ELMOD2	ENST00000513606.1	c.168+4A>C		splice_donor_region_variant, intron_variant		4
ELMOD2	ENST00000512057.1	n.544+4A>C		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 291 AN: 152054 Hom.: 6 Cov.: 32

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

GnomAD3 exomes AF: 0.00504 AC: 1193 AN: 236620 Hom.: 21 AF XY: 0.00559 AC XY: 717 AN XY: 128176

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 SAS exome AF: 0.0215

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.: 56 Cov.: 30 AF XY: 0.00273 AC XY: 1963 AN XY: 718312

Gnomad4 AFR exome AF: 0.0000928

Gnomad4 AMR exome AF: 0.0000952

Gnomad4 ASJ exome AF: 0.00421

Gnomad4 EAS exome AF: 0.0251

Gnomad4 SAS exome AF: 0.0216

Gnomad4 FIN exome AF: 0.0000942

Gnomad4 NFE exome AF: 0.000138

Gnomad4 OTH exome AF: 0.00388

GnomAD4 genome AF: 0.00191 AC: 290 AN: 152172 Hom.: 6 Cov.: 32 AF XY: 0.00249 AC XY: 185 AN XY: 74394

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.0279

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000779 Hom.: 1

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

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

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	19
Dann	Benign	0.97

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

LitVar

Other links and lift over

dbSNP: rs149594258; hg19: chr4-141458699;