rs4315920

chr5-139409996-G-A

Variant summary

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

The ENST00000515559.2(DNAJC18):c.*85-1134C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,064 control chromosomes in the GnomAD database, including 26,387 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 0.57 (26387 hom., cov: 32)
• Consequence: DNAJC18 ENST00000515559.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

Genes affected

DNAJC18 (HGNC:28429): (DnaJ heat shock protein family (Hsp40) member C18) Predicted to enable Hsp70 protein binding activity. Predicted to be involved in cellular response to misfolded protein; chaperone cofactor-dependent protein refolding; and ubiquitin-dependent ERAD pathway. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC18	ENST00000515559.2	c.*85-1134C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86154 AN: 151944 Hom.: 26381 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.567 AC: 86189 AN: 152064 Hom.: 26387 Cov.: 32 AF XY: 0.564 AC XY: 41895 AN XY: 74308

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.564

Alfa AF: 0.644 Hom.: 11368

Bravo AF: 0.550

Asia WGS AF: 0.453 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.0
Dann	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4315920; hg19: chr5-138745685;