18-50979044-C-T

Variant names:

• chr18-50979044-C-T
• rs2027735
• NM_018696.3:c.157+4483C>T

Variant summary

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

The NM_018696.3(ELAC1):​c.157+4483C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,060 control chromosomes in the GnomAD database, including 10,679 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 0.37 (10679 hom., cov: 32)
• Consequence: ELAC1 NM_018696.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 3 publications found

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]

ENSG00000267699 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAC1	NM_018696.3	c.157+4483C>T		intron_variant	Intron 2 of 3	ENST00000269466.8	NP_061166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAC1	ENST00000269466.8	c.157+4483C>T		intron_variant	Intron 2 of 3	1	NM_018696.3	ENSP00000269466.3
ENSG00000267699	ENST00000590722.2	n.157+4483C>T		intron_variant	Intron 2 of 8	2		ENSP00000465737.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56534 AN: 151942 Hom.: 10678 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.372 AC: 56571 AN: 152060 Hom.: 10679 Cov.: 32 AF XY: 0.370 AC XY: 27528 AN XY: 74338

African (AFR) AF: 0.346 AC: 14367 AN: 41480

American (AMR) AF: 0.380 AC: 5810 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1352 AN: 3468

East Asian (EAS) AF: 0.451 AC: 2326 AN: 5158

South Asian (SAS) AF: 0.239 AC: 1151 AN: 4822

European-Finnish (FIN) AF: 0.409 AC: 4321 AN: 10562

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25750 AN: 67978

Other (OTH) AF: 0.386 AC: 816 AN: 2112

Alfa AF: 0.382 Hom.: 14367

Bravo AF: 0.377

Asia WGS AF: 0.358 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.6
DANN	Benign	0.66
PhyloP100		-0.0020
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: rs2027735; hg19: chr18-48505414;