NM_153702.4:c.*9C>T

Variant names:

• chr4-140550384-C-T
• rs75824346
• NM_153702.4:c.*9C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_153702.4(ELMOD2):​c.*9C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,585,338 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (25 hom.)
• Consequence: ELMOD2 NM_153702.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0870
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-140550384-C-T is Benign according to our data. Variant chr4-140550384-C-T is described in ClinVar as Benign. ClinVar VariationId is 226629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00137 (1961/1433032) while in subpopulation AMR AF = 0.0259 (999/38644). AF 95% confidence interval is 0.0245. There are 25 homozygotes in GnomAdExome4. There are 880 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMOD2	NM_153702.4	MANE Select	c.*9C>T		3_prime_UTR	Exon 9 of 9	NP_714913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMOD2	ENST00000323570.8	TSL:1 MANE Select	c.*9C>T		3_prime_UTR	Exon 9 of 9	ENSP00000326342.3
	ELMOD2	ENST00000502290.1	TSL:3	n.507C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 344 AN: 152188 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00566 AC: 1299 AN: 229676 AF XY: 0.00452

Gnomad AFR exome AF: 0.000922

Gnomad AMR exome AF: 0.0311

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0150

Gnomad FIN exome AF: 0.00211

Gnomad NFE exome AF: 0.000584

Gnomad OTH exome AF: 0.00289

GnomAD4 exome AF: 0.00137 AC: 1961 AN: 1433032 Hom.: 25 Cov.: 30 AF XY: 0.00124 AC XY: 880 AN XY: 711762

African (AFR) AF: 0.000438 AC: 14 AN: 31966

American (AMR) AF: 0.0259 AC: 999 AN: 38644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25144

East Asian (EAS) AF: 0.0118 AC: 462 AN: 39010

South Asian (SAS) AF: 0.00102 AC: 83 AN: 81148

European-Finnish (FIN) AF: 0.00208 AC: 109 AN: 52368

Middle Eastern (MID) AF: 0.000438 AC: 2 AN: 4566

European-Non Finnish (NFE) AF: 0.000189 AC: 208 AN: 1101060

Other (OTH) AF: 0.00142 AC: 84 AN: 59126

GnomAD4 genome AF: 0.00225 AC: 343 AN: 152306 Hom.: 3 Cov.: 32 AF XY: 0.00258 AC XY: 192 AN XY: 74462

African (AFR) AF: 0.000746 AC: 31 AN: 41580

American (AMR) AF: 0.0123 AC: 188 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68024

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00118 Hom.: 0

Bravo AF: 0.00371

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 12, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

*9C>T in exon 9 of ELMOD2: This variant is not expected to have clinical signifi cance because it has been identified in 3.0% (359/11216), including 5 homozygote s of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs75824346).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.57
PhyloP100		-0.087
Mutation Taster		=100/0	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: rs75824346; hg19: chr4-141471538;