rs10163789

Positions:

• chr18-50968992-G-A
• chr18-50968992-G-C

Variant summary

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

The NM_018696.3(ELAC1):​c.-9+878G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 152,300 control chromosomes in the GnomAD database, including 65,250 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 0.92 (65248 hom., cov: 33)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: ELAC1 NM_018696.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

Genes affected

ELAC1 (HGNC:14197): (elaC ribonuclease Z 1) Predicted to enable 3'-tRNA processing endoribonuclease activity. Predicted to be involved in tRNA 3'-trailer cleavage, endonucleolytic. Located in cytosol and nucleoplasm. [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 (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAC1	NM_018696.3	c.-9+878G>A		intron_variant		ENST00000269466.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAC1	ENST00000269466.8	c.-9+878G>A		intron_variant		1	NM_018696.3	P1
ELAC1	ENST00000591429.1	c.-9+878G>A		intron_variant		1
ELAC1	ENST00000588577.5	c.-9+878G>A		intron_variant		2
ELAC1	ENST00000586966.2	n.631G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140713 AN: 152178 Hom.: 65196 Cov.: 33

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.931

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.925 AC: 140826 AN: 152296 Hom.: 65248 Cov.: 33 AF XY: 0.922 AC XY: 68631 AN XY: 74462

Gnomad4 AFR AF: 0.983

Gnomad4 AMR AF: 0.897

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.910

Gnomad4 OTH AF: 0.931

Alfa AF: 0.912 Hom.: 82478

Bravo AF: 0.929

Asia WGS AF: 0.889 AC: 3090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.62

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: rs10163789; hg19: chr18-48495362;