rs2066271

Positions:

• chr10-21858494-C-T

Variant summary

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

The NM_022365.4(DNAJC1):​c.978+23788G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,130 control chromosomes in the GnomAD database, including 43,163 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 0.75 (43163 hom., cov: 32)
• Consequence: DNAJC1 NM_022365.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

Genes affected

DNAJC1 (HGNC:20090): (DnaJ heat shock protein family (Hsp40) member C1) The membrane protein encoded by this gene is a DNAJ-like heat shock protein that binds the molecular chaperone BiP. In addition, the encoded protein contains two SANT domains that have been shown to bind serpin alpha1-antichymotrypsin and inter-alpha trypsin inhibitor heavy chain 4. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC1	NM_022365.4	c.978+23788G>A		intron_variant		ENST00000376980.8
DNAJC1	XM_011519614.4	c.978+23788G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC1	ENST00000376980.8	c.978+23788G>A		intron_variant		1	NM_022365.4	P1
DNAJC1	ENST00000483085.1	n.163+2250G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113538 AN: 152012 Hom.: 43118 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.747 AC: 113636 AN: 152130 Hom.: 43163 Cov.: 32 AF XY: 0.747 AC XY: 55547 AN XY: 74368

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.703

Alfa AF: 0.697 Hom.: 13239

Bravo AF: 0.749

Asia WGS AF: 0.854 AC: 2970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.57

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: rs2066271; hg19: chr10-22147423;