rs2807982

chr10-21926931-T-Achr10-21926931-T-Cchr10-21926931-T-G

Variant summary

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

The NM_022365.4(DNAJC1):c.371+1575A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,014 control chromosomes in the GnomAD database, including 31,595 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 0.64 (31595 hom., cov: 33)
• Consequence: DNAJC1 NM_022365.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740

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 = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC1	NM_022365.4	c.371+1575A>T		intron_variant		ENST00000376980.8
DNAJC1	XM_011519614.4	c.371+1575A>T		intron_variant
DNAJC1	XM_017016536.3	c.371+1575A>T		intron_variant
DNAJC1	XM_047425628.1	c.371+1575A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC1	ENST00000376980.8	c.371+1575A>T		intron_variant		1	NM_022365.4	P1
DNAJC1	ENST00000476103.3	c.324+2109A>T		intron_variant, NMD_transcript_variant		2
DNAJC1	ENST00000376946.2	n.659+2109A>T		intron_variant, non_coding_transcript_variant		3
DNAJC1	ENST00000447548.5	n.336+1575A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97052 AN: 151896 Hom.: 31577 Cov.: 33

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.639 AC: 97116 AN: 152014 Hom.: 31595 Cov.: 33 AF XY: 0.641 AC XY: 47646 AN XY: 74322

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.608

Alfa AF: 0.551 Hom.: 1606

Bravo AF: 0.631

Asia WGS AF: 0.784 AC: 2723 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.4
Dann	Benign	0.44

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: rs2807982; hg19: chr10-22215860;