rs3733160

Variant names:

• chr3-186571021-G-A
• rs3733160
• NM_016306.6:c.68+56G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-186571021-G-A
• chr3-186571021-G-C
• chr3-186571021-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016306.6(DNAJB11):​c.68+56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,003,232 control chromosomes in the GnomAD database, including 11,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4436 hom., cov: 28)
  • Exomes 𝑓: 0.092 (7495 hom.)
• Consequence: DNAJB11 NM_016306.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.50
• Publications: 5 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: Orphanet, ClinGen
• polycystic kidney disease 6 with or without polycystic liver disease

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

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-186571021-G-A is Benign according to our data. Variant chr3-186571021-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 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.68+56G>A		intron	N/A	NP_057390.1	Q9UBS4
	DNAJB11	NM_001378451.1		c.68+56G>A		intron	N/A	NP_001365380.1
	DNAJB11	NR_165638.1		n.246+56G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB11	ENST00000265028.8	TSL:1 MANE Select	c.68+56G>A		intron	N/A	ENSP00000265028.3	Q9UBS4
	DNAJB11	ENST00000439351.5	TSL:1	c.68+56G>A		intron	N/A	ENSP00000414398.1	Q9UBS4
	DNAJB11	ENST00000956498.1		c.68+56G>A		intron	N/A	ENSP00000626557.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32349 AN: 150378 Hom.: 4425 Cov.: 28

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.0924 AC: 78796 AN: 852738 Hom.: 7495 AF XY: 0.0980 AC XY: 42382 AN XY: 432548

African (AFR) AF: 0.303 AC: 4356 AN: 14370

American (AMR) AF: 0.147 AC: 2933 AN: 19976

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 2863 AN: 18970

East Asian (EAS) AF: 0.141 AC: 4019 AN: 28504

South Asian (SAS) AF: 0.207 AC: 12159 AN: 58654

European-Finnish (FIN) AF: 0.166 AC: 7573 AN: 45614

Middle Eastern (MID) AF: 0.185 AC: 762 AN: 4124

European-Non Finnish (NFE) AF: 0.0635 AC: 39623 AN: 624290

Other (OTH) AF: 0.118 AC: 4508 AN: 38236

GnomAD4 genome AF: 0.215 AC: 32390 AN: 150494 Hom.: 4436 Cov.: 28 AF XY: 0.217 AC XY: 15951 AN XY: 73460

African (AFR) AF: 0.390 AC: 15840 AN: 40626

American (AMR) AF: 0.197 AC: 2998 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3464

East Asian (EAS) AF: 0.141 AC: 711 AN: 5052

South Asian (SAS) AF: 0.235 AC: 1113 AN: 4738

European-Finnish (FIN) AF: 0.175 AC: 1814 AN: 10376

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8704 AN: 67768

Other (OTH) AF: 0.212 AC: 440 AN: 2080

Alfa AF: 0.194 Hom.: 411

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.4
DANN	Benign	0.94
PhyloP100		1.5
PromoterAI		0.11	Neutral
Mutation Taster		=20/80	disease causing

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

Other links and lift over

dbSNP: rs3733160; hg19: chr3-186288810; COSMIC: COSV54002164; COSMIC: COSV54002164;