rs28618174

Variant names:

• chr17-41990103-C-T
• rs28618174
• NM_003315.4:c.599+161G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-41990103-C-T
• chr17-41990103-C-G

Variant summary

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

The NM_003315.4(DNAJC7):​c.599+161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,102 control chromosomes in the GnomAD database, including 13,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.41 (13877 hom., cov: 33)
• Consequence: DNAJC7 NM_003315.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.226
• Publications: 0 publications found

Genes affected

DNAJC7 (HGNC:12392): (DnaJ heat shock protein family (Hsp40) member C7) This gene encodes a member of the DNAJ heat shock protein 40 family of proteins that is characterized by two N-terminal tetratricopeptide repeat domains and a C-terminal DNAJ domain. This protein binds the chaperone proteins heat shock proteins 70 and 90 in an ATP-dependent manner and may function as a co-chaperone. Pseudogenes of this gene are found on chromosomes 1 and 6. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

DNAJC7 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-41990103-C-T is Benign according to our data. Variant chr17-41990103-C-T is described in ClinVar as Benign. ClinVar VariationId is 1223976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003315.4. 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
	DNAJC7	NM_003315.4	MANE Select	c.599+161G>A		intron	N/A	NP_003306.3	Q99615-1
	DNAJC7	NM_001144766.3		c.431+161G>A		intron	N/A	NP_001138238.1	Q99615-2
	DNAJC7	NR_029431.2		n.533+161G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC7	ENST00000457167.9	TSL:1 MANE Select	c.599+161G>A		intron	N/A	ENSP00000406463.2	Q99615-1
	DNAJC7	ENST00000316603.12	TSL:1	c.431+161G>A		intron	N/A	ENSP00000313311.7	Q99615-2
	DNAJC7	ENST00000589810.5	TSL:1	n.431+161G>A		intron	N/A	ENSP00000467477.1	K7EPP7

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61611 AN: 151984 Hom.: 13877 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.405 AC: 61614 AN: 152102 Hom.: 13877 Cov.: 33 AF XY: 0.405 AC XY: 30098 AN XY: 74338

African (AFR) AF: 0.205 AC: 8505 AN: 41490

American (AMR) AF: 0.413 AC: 6309 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1945 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2324 AN: 5174

South Asian (SAS) AF: 0.567 AC: 2735 AN: 4826

European-Finnish (FIN) AF: 0.431 AC: 4553 AN: 10566

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33867 AN: 67980

Other (OTH) AF: 0.417 AC: 881 AN: 2114

Alfa AF: 0.453 Hom.: 5996

Bravo AF: 0.390

Asia WGS AF: 0.455 AC: 1582 AN: 3478

ClinVar

ClinVar submissions

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	-0.85
CADD	Benign	5.7
DANN	Benign	0.69
PhyloP100		-0.23
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: rs28618174; hg19: chr17-40142121; COSMIC: COSV57270291; COSMIC: COSV57270291;