rs2195731

Variant names:

• chr9-23785969-C-A
• rs2195731
• NM_004432.5:c.-15-23720G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004432.5(ELAVL2):​c.-15-23720G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 152,176 control chromosomes in the GnomAD database, including 963 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 0.095 (963 hom., cov: 32)
• Consequence: ELAVL2 NM_004432.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004432.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAVL2	NM_004432.5	MANE Select	c.-15-23720G>T		intron	N/A	NP_004423.2	Q12926-1
	ELAVL2	NM_001351455.2		c.-19-20870G>T		intron	N/A	NP_001338384.1	A0A0A0MRX1
	ELAVL2	NM_001385697.1		c.-19-20870G>T		intron	N/A	NP_001372626.1	A0A0A0MRX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAVL2	ENST00000397312.7	TSL:1 MANE Select	c.-15-23720G>T		intron	N/A	ENSP00000380479.2	Q12926-1
	ELAVL2	ENST00000380117.5	TSL:1	c.-12-23723G>T		intron	N/A	ENSP00000369460.1	Q12926-1
	ELAVL2	ENST00000223951.10	TSL:1	c.-15-23720G>T		intron	N/A	ENSP00000223951.5	Q12926-2

Frequencies

GnomAD3 genomes AF: 0.0950 AC: 14439 AN: 152058 Hom.: 947 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.0953 AC: 14499 AN: 152176 Hom.: 963 Cov.: 32 AF XY: 0.0975 AC XY: 7255 AN XY: 74396

African (AFR) AF: 0.128 AC: 5296 AN: 41530

American (AMR) AF: 0.182 AC: 2778 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3472

East Asian (EAS) AF: 0.171 AC: 884 AN: 5158

South Asian (SAS) AF: 0.0951 AC: 459 AN: 4824

European-Finnish (FIN) AF: 0.0575 AC: 610 AN: 10604

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0543 AC: 3692 AN: 68012

Other (OTH) AF: 0.115 AC: 242 AN: 2110

Alfa AF: 0.0775 Hom.: 1038

Bravo AF: 0.110

Asia WGS AF: 0.136 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.75
PhyloP100		0.16
Mutation Taster		=100/0	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: rs2195731; hg19: chr9-23785967;