chr9-23769756-A-C

Position:

• chr9-23769756-A-C

Variant summary

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

The NM_004432.5(ELAVL2):​c.-15-7507T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0881 in 152,258 control chromosomes in the GnomAD database, including 675 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.088 (675 hom., cov: 32)
• Consequence: ELAVL2 NM_004432.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769

Genes affected

ELAVL2 (HGNC:3313): (ELAV like RNA binding protein 2) In humans, the ELAV like RNA binding protein gene family has four members (ELAVL1-4). ELAVL RNA binding proteins recognize AU-rich elements in the 3' UTRs of gene transcripts and thereby regulate gene expression post-transcriptionally. The protein encoded by this gene binds to several 3' UTRs, including its own and also that of FOS, ID, and POU5F1. This gene encodes ELAVL2 and, like ELAVL3 and ELAVL4, is expressed specifically in neurons and primarily localizes to the cytoplasm. This protein also forms a cytosolic complex with the normally nuclear-localized ELAVL1 protein. Alternative splicing of this gene results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAVL2	NM_004432.5	c.-15-7507T>G		intron_variant		ENST00000397312.7	NP_004423.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAVL2	ENST00000397312.7	c.-15-7507T>G		intron_variant		1	NM_004432.5	ENSP00000380479

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13401 AN: 152140 Hom.: 675 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.0896

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0881 AC: 13418 AN: 152258 Hom.: 675 Cov.: 32 AF XY: 0.0908 AC XY: 6758 AN XY: 74442

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0966

Gnomad4 FIN AF: 0.0896

Gnomad4 NFE AF: 0.0752

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0463 Hom.: 44

Bravo AF: 0.0929

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.0
DANN	Benign	0.71

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: rs10491817; hg19: chr9-23769754;