rs2066271

Variant names:

• chr10-21858494-C-T
• rs2066271
• NM_022365.4:c.978+23788G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNAJC1	NM_022365.4	c.978+23788G>A		intron_variant	Intron 8 of 11	ENST00000376980.8	NP_071760.2
DNAJC1	XM_011519614.4	c.978+23788G>A		intron_variant	Intron 8 of 9		XP_011517916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC1	ENST00000376980.8	c.978+23788G>A		intron_variant	Intron 8 of 11	1	NM_022365.4	ENSP00000366179.3
DNAJC1	ENST00000483085.1	n.163+2250G>A		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.861 AC: 35778 AN: 41540

American (AMR) AF: 0.681 AC: 10397 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1763 AN: 3470

East Asian (EAS) AF: 0.986 AC: 5116 AN: 5188

South Asian (SAS) AF: 0.796 AC: 3836 AN: 4822

European-Finnish (FIN) AF: 0.701 AC: 7405 AN: 10566

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47223 AN: 67968

Other (OTH) AF: 0.703 AC: 1484 AN: 2112

Alfa AF: 0.700 Hom.: 20962

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
PhyloP100		-0.69
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: rs2066271; hg19: chr10-22147423;