chr1-50195592-T-G

Position:

• chr1-50195592-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001144774.3(ELAVL4):​c.540T>G​(p.Phe180Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELAVL4 NM_001144774.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.96

Genes affected

ELAVL4 (HGNC:3315): (ELAV like RNA binding protein 4) Enables mRNA 3'-UTR AU-rich region binding activity; poly(A) binding activity; and pre-mRNA intronic pyrimidine-rich binding activity. Involved in 3'-UTR-mediated mRNA stabilization; RNA processing; and positive regulation of 3'-UTR-mediated mRNA stabilization. Predicted to be located in axon; cytoplasm; and dendrite. Predicted to be part of polysomal ribosome. Predicted to be active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAVL4	NM_001144774.3	c.540T>G	p.Phe180Leu	missense_variant	5/7	ENST00000371824.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAVL4	ENST00000371824.7	c.540T>G	p.Phe180Leu	missense_variant	5/7	1	NM_001144774.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Jun 02, 2021

Gene of uncertain significance -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	.;.;.;.;T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.3	.;M;.;M;M;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.6	D;D;.;D;D;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D;D;.;D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D;D;D;D
Polyphen		0.99, 1.0, 1.0, 1.0	.;D;.;D;D;D;D
Vest4		0.94
MutPred		0.76		.;.;.;.;.;Loss of ubiquitination at K187 (P = 0.0818);Loss of ubiquitination at K187 (P = 0.0818);
MVP		0.87
MPC		2.1
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.92
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-50661264;