3-186581318-G-A

Position:

• chr3-186581318-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016306.6(DNAJB11):​c.457-53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,598,236 control chromosomes in the GnomAD database, including 10,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1787 hom., cov: 31)
  • Exomes 𝑓: 0.10 (8716 hom.)
• Consequence: DNAJB11 NM_016306.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13

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]

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-186581318-G-A is Benign according to our data. Variant chr3-186581318-G-A is described in ClinVar as [Benign]. Clinvar id is 1233131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB11	NM_016306.6	c.457-53G>A		intron_variant		ENST00000265028.8	NP_057390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB11	ENST00000265028.8	c.457-53G>A		intron_variant		1	NM_016306.6	ENSP00000265028	P1
HRG-AS1	ENST00000630178.2	n.239-1352C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21421 AN: 151732 Hom.: 1784 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.100 AC: 144757 AN: 1446386 Hom.: 8716 Cov.: 29 AF XY: 0.102 AC XY: 73404 AN XY: 718774

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.0807

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.141 AC: 21436 AN: 151850 Hom.: 1787 Cov.: 31 AF XY: 0.146 AC XY: 10847 AN XY: 74190

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.0870

Gnomad4 OTH AF: 0.139

Alfa AF: 0.104 Hom.: 989

Bravo AF: 0.142

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.43
DANN	Benign	0.18

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: rs11921733; hg19: chr3-186299107;