4-140540016-A-T

Position:

• chr4-140540016-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153702.4(ELMOD2):​c.400-152A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 807,802 control chromosomes in the GnomAD database, including 6,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1668 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4511 hom.)
• Consequence: ELMOD2 NM_153702.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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]

ELMOD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 4-140540016-A-T is Benign according to our data. Variant chr4-140540016-A-T is described in ClinVar as [Benign]. Clinvar id is 1235681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD2	NM_153702.4	c.400-152A>T		intron_variant		ENST00000323570.8	NP_714913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMOD2	ENST00000323570.8	c.400-152A>T		intron_variant		1	NM_153702.4	ENSP00000326342.3
ELMOD2	ENST00000502397.5	c.400-152A>T		intron_variant		5		ENSP00000422582.1
ELMOD2	ENST00000513606.1	c.169-152A>T		intron_variant		4		ENSP00000427592.1
ELMOD2	ENST00000512057.1	n.545-152A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21478 AN: 152098 Hom.: 1668 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.113 AC: 73795 AN: 655586 Hom.: 4511 AF XY: 0.113 AC XY: 37570 AN XY: 331910

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.0909

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.141 AC: 21494 AN: 152216 Hom.: 1668 Cov.: 32 AF XY: 0.142 AC XY: 10550 AN XY: 74414

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0937

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.143

Alfa AF: 0.0536 Hom.: 62

Bravo AF: 0.152

Asia WGS AF: 0.182 AC: 630 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs16998469; hg19: chr4-141461170;