rs2494876

Variant names:

• chr1-50200843-C-T
• rs2494876
• ENST00000371823.8:c.808C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ELAVL4	NM_001144774.3	c.774-8C>T		splice_region_variant, intron_variant	Intron 6 of 6	ENST00000371824.7	NP_001138246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAVL4	ENST00000371824.7	c.774-8C>T		splice_region_variant, intron_variant	Intron 6 of 6	1	NM_001144774.3	ENSP00000360889.2

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

GnomAD2 exomes AF: 0.846 AC: 210506 AN: 248888 AF XY: 0.857

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 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

African (AFR) AF: 0.397 AC: 13253 AN: 33422

American (AMR) AF: 0.874 AC: 38860 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 23807 AN: 25960

East Asian (EAS) AF: 0.692 AC: 27456 AN: 39674

South Asian (SAS) AF: 0.884 AC: 75653 AN: 85602

European-Finnish (FIN) AF: 0.842 AC: 44904 AN: 53336

Middle Eastern (MID) AF: 0.923 AC: 5300 AN: 5744

European-Non Finnish (NFE) AF: 0.923 AC: 1025347 AN: 1110418

Other (OTH) AF: 0.872 AC: 52538 AN: 60282

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

African (AFR) AF: 0.414 AC: 17084 AN: 41230

American (AMR) AF: 0.875 AC: 13317 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3184 AN: 3470

East Asian (EAS) AF: 0.651 AC: 3308 AN: 5084

South Asian (SAS) AF: 0.878 AC: 4188 AN: 4772

European-Finnish (FIN) AF: 0.822 AC: 8610 AN: 10472

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62279 AN: 67924

Other (OTH) AF: 0.820 AC: 1722 AN: 2100

Alfa AF: 0.835 Hom.: 88666

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;.
PhyloP100		0.85
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
Mutation Taster		=99/1	polymorphism (auto)

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