rs2666781

Positions:

• chr10-21916747-C-A

Variant summary

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

The NM_022365.4(DNAJC1):​c.729+2032G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,866 control chromosomes in the GnomAD database, including 27,885 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 0.59 (27885 hom., cov: 31)
• Consequence: DNAJC1 NM_022365.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC1	NM_022365.4	c.729+2032G>T		intron_variant		ENST00000376980.8	NP_071760.2
DNAJC1	XM_011519614.4	c.729+2032G>T		intron_variant			XP_011517916.1
DNAJC1	XM_017016536.3	c.729+2032G>T		intron_variant			XP_016872025.1
DNAJC1	XM_047425628.1	c.729+2032G>T		intron_variant			XP_047281584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC1	ENST00000376980.8	c.729+2032G>T		intron_variant		1	NM_022365.4	ENSP00000366179	P1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89203 AN: 151748 Hom.: 27883 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.587 AC: 89220 AN: 151866 Hom.: 27885 Cov.: 31 AF XY: 0.592 AC XY: 43915 AN XY: 74226

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.560

Alfa AF: 0.618 Hom.: 3843

Bravo AF: 0.570

Asia WGS AF: 0.772 AC: 2677 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2666781; hg19: chr10-22205676;