rs2494876

Positions:

• chr1-50200843-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000371823.8(ELAVL4):​c.808C>T​(p.Pro270Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 1,610,364 control chromosomes in the GnomAD database, including 638,891 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (47221 hom., cov: 28)
  • Exomes 𝑓: 0.90 (591670 hom.)
• Consequence: ELAVL4 ENST00000371823.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.846

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.7302653E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAVL4	NM_001144774.3	c.774-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000371824.7	NP_001138246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAVL4	ENST00000371824.7	c.774-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001144774.3	ENSP00000360889	P4

Frequencies

GnomAD3 genomes AF: 0.759 AC: 114820 AN: 151358 Hom.: 47216 Cov.: 28

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.983

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.822

GnomAD3 exomes AF: 0.846 AC: 210506 AN: 248888 Hom.: 91507 AF XY: 0.857 AC XY: 115217 AN XY: 134378

Gnomad AFR exome AF: 0.405

Gnomad AMR exome AF: 0.873

Gnomad ASJ exome AF: 0.918

Gnomad EAS exome AF: 0.638

Gnomad SAS exome AF: 0.886

Gnomad FIN exome AF: 0.839

Gnomad NFE exome AF: 0.917

Gnomad OTH exome AF: 0.886

GnomAD4 exome AF: 0.896 AC: 1307118 AN: 1458888 Hom.: 591670 Cov.: 56 AF XY: 0.897 AC XY: 650832 AN XY: 725416

Gnomad4 AFR exome AF: 0.397

Gnomad4 AMR exome AF: 0.874

Gnomad4 ASJ exome AF: 0.917

Gnomad4 EAS exome AF: 0.692

Gnomad4 SAS exome AF: 0.884

Gnomad4 FIN exome AF: 0.842

Gnomad4 NFE exome AF: 0.923

Gnomad4 OTH exome AF: 0.872

GnomAD4 genome AF: 0.758 AC: 114842 AN: 151476 Hom.: 47221 Cov.: 28 AF XY: 0.758 AC XY: 56035 AN XY: 73958

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.820

Alfa AF: 0.878 Hom.: 60043

Bravo AF: 0.747

TwinsUK AF: 0.923 AC: 3424

ALSPAC AF: 0.924 AC: 3561

ESP6500AA AF: 0.429 AC: 1891

ESP6500EA AF: 0.921 AC: 7917

ExAC AF: 0.839 AC: 101875

Asia WGS AF: 0.741 AC: 2578 AN: 3478

EpiCase AF: 0.921

EpiControl AF: 0.921

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.65
DEOGEN2	Benign	0.087	T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.42	T;T
MetaRNN	Benign	6.7e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.42	N;N
REVEL	Benign	0.051
Sift	Benign	0.80	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.0010	B;.
Vest4		0.091
ClinPred		0.0059	T
GERP RS		3.5
Varity_R		0.033

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: rs2494876; hg19: chr1-50666515; COSMIC: COSV63917207; COSMIC: COSV63917207;