3-186571884-T-G

Variant names:

• chr3-186571884-T-G
• rs713484
• NM_016306.6:c.69-211T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016306.6(DNAJB11):​c.69-211T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,160 control chromosomes in the GnomAD database, including 6,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (6778 hom., cov: 33)
• Consequence: DNAJB11 NM_016306.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.14
• Publications: 2 publications found

Genes affected

DNAJB11 (HGNC:14889): (DnaJ heat shock protein family (Hsp40) member B11) This gene encodes a soluble glycoprotein of the endoplasmic reticulum (ER) lumen that functions as a co-chaperone of binding immunoglobulin protein, a 70 kilodalton heat shock protein chaperone required for the proper folding and assembly of proteins in the ER. The encoded protein contains a highly conserved J domain of about 70 amino acids with a characteristic His-Pro-Asp (HPD) motif and may regulate the activity of binding immunoglobulin protein by stimulating ATPase activity. [provided by RefSeq, Mar 2014]

DNAJB11 Gene-Disease associations (from GenCC):

• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• polycystic kidney disease 6 with or without polycystic liver disease

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-186571884-T-G is Benign according to our data. Variant chr3-186571884-T-G is described in ClinVar as Benign. ClinVar VariationId is 1275544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016306.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB11	NM_016306.6	MANE Select	c.69-211T>G		intron	N/A	NP_057390.1	Q9UBS4
	DNAJB11	NM_001378451.1		c.69-211T>G		intron	N/A	NP_001365380.1
	DNAJB11	NR_165638.1		n.247-211T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB11	ENST00000265028.8	TSL:1 MANE Select	c.69-211T>G		intron	N/A	ENSP00000265028.3	Q9UBS4
	DNAJB11	ENST00000439351.5	TSL:1	c.69-211T>G		intron	N/A	ENSP00000414398.1	Q9UBS4
	DNAJB11	ENST00000956498.1		c.69-211T>G		intron	N/A	ENSP00000626557.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40400 AN: 152042 Hom.: 6757 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.266 AC: 40458 AN: 152160 Hom.: 6778 Cov.: 33 AF XY: 0.266 AC XY: 19816 AN XY: 74392

African (AFR) AF: 0.474 AC: 19660 AN: 41472

American (AMR) AF: 0.236 AC: 3608 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3470

East Asian (EAS) AF: 0.149 AC: 771 AN: 5188

South Asian (SAS) AF: 0.250 AC: 1206 AN: 4826

European-Finnish (FIN) AF: 0.213 AC: 2255 AN: 10584

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11464 AN: 68016

Other (OTH) AF: 0.270 AC: 569 AN: 2110

Alfa AF: 0.241 Hom.: 986

Bravo AF: 0.275

Asia WGS AF: 0.209 AC: 727 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.46
PhyloP100		1.1
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: rs713484; hg19: chr3-186289673;