chr19-14514978-G-A

Variant names:

• chr19-14514978-G-A
• rs7003
• NM_006145.3:c.*962C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006145.3(DNAJB1):​c.*962C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,430 control chromosomes in the GnomAD database, including 2,000 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 0.15 (1998 hom., cov: 32)
  • Exomes 𝑓: 0.095 (2 hom.)
• Consequence: DNAJB1 NM_006145.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• Publications: 14 publications found

Genes affected

DNAJB1 (HGNC:5270): (DnaJ heat shock protein family (Hsp40) member B1) This gene encodes a member of the DnaJ or Hsp40 (heat shock protein 40 kD) family of proteins. DNAJ family members are characterized by a highly conserved amino acid stretch called the 'J-domain' and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. The encoded protein is a molecular chaperone that stimulates the ATPase activity of Hsp70 heat-shock proteins in order to promote protein folding and prevent misfolded protein aggregation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006145.3. 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
	DNAJB1	NM_006145.3	MANE Select	c.*962C>T		3_prime_UTR	Exon 3 of 3	NP_006136.1	Q6FHS4
	DNAJB1	NM_001300914.2		c.*962C>T		3_prime_UTR	Exon 3 of 3	NP_001287843.1	P25685-2
	DNAJB1	NM_001313964.2		c.*962C>T		3_prime_UTR	Exon 4 of 4	NP_001300893.1	P25685-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB1	ENST00000254322.3	TSL:1 MANE Select	c.*962C>T		3_prime_UTR	Exon 3 of 3	ENSP00000254322.1	P25685-1
	DNAJB1	ENST00000595139.2	TSL:4	c.*1458C>T		3_prime_UTR	Exon 2 of 2	ENSP00000469221.2	M0QXK0
	DNAJB1	ENST00000676577.1		c.*962C>T		3_prime_UTR	Exon 3 of 3	ENSP00000503351.1	A0A7I2V3K7

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23549 AN: 151932 Hom.: 1999 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0756

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.0947 AC: 36 AN: 380 Hom.: 2 Cov.: 0 AF XY: 0.0938 AC XY: 21 AN XY: 224

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0946 AC: 35 AN: 370

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.155 AC: 23560 AN: 152050 Hom.: 1998 Cov.: 32 AF XY: 0.151 AC XY: 11242 AN XY: 74328

African (AFR) AF: 0.216 AC: 8943 AN: 41446

American (AMR) AF: 0.135 AC: 2062 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0756 AC: 262 AN: 3466

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5182

South Asian (SAS) AF: 0.137 AC: 660 AN: 4814

European-Finnish (FIN) AF: 0.109 AC: 1154 AN: 10564

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9893 AN: 67990

Other (OTH) AF: 0.158 AC: 335 AN: 2114

Alfa AF: 0.148 Hom.: 2172

Bravo AF: 0.160

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.75
PhyloP100		-0.72
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
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: rs7003; hg19: chr19-14625790;