rs3802100

Variant names:

• chr7-157358540-C-T
• rs3802100
• NM_058246.4:c.-26-7C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-157358540-C-T
• chr7-157358540-C-A
• chr7-157358540-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_058246.4(DNAJB6):​c.-26-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,596,402 control chromosomes in the GnomAD database, including 262,231 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23231 hom., cov: 31)
  • Exomes 𝑓: 0.57 (239000 hom.)
• Consequence: DNAJB6 NM_058246.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002081
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.543
• Publications: 10 publications found

Genes affected

DNAJB6 (HGNC:14888): (DnaJ heat shock protein family (Hsp40) member B6) This gene encodes a member of the DNAJ protein family. 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. This family member may also play a role in polyglutamine aggregation in specific neurons. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

DNAJB6 Gene-Disease associations (from GenCC):

• muscular dystrophy, limb-girdle, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-157358540-C-T is Benign according to our data. Variant chr7-157358540-C-T is described in ClinVar as Benign. ClinVar VariationId is 262304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058246.4. 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
	DNAJB6	NM_058246.4	MANE Select	c.-26-7C>T		splice_region intron	N/A	NP_490647.1	O75190-1
	DNAJB6	NM_005494.3		c.-26-7C>T		splice_region intron	N/A	NP_005485.1	O75190-2
	DNAJB6	NM_001363676.1		c.-26-7C>T		splice_region intron	N/A	NP_001350605.1	E9PH18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB6	ENST00000262177.9	TSL:1 MANE Select	c.-26-7C>T		splice_region intron	N/A	ENSP00000262177.4	O75190-1
	DNAJB6	ENST00000429029.6	TSL:1	c.-26-7C>T		splice_region intron	N/A	ENSP00000397556.2	O75190-2
	DNAJB6	ENST00000459889.5	TSL:1	n.-26-7C>T		splice_region intron	N/A	ENSP00000488263.1	A0A0J9YX62

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83223 AN: 151798 Hom.: 23188 Cov.: 31

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.572

GnomAD2 exomes AF: 0.578 AC: 144571 AN: 250318 AF XY: 0.575

Gnomad AFR exome AF: 0.454

Gnomad AMR exome AF: 0.616

Gnomad ASJ exome AF: 0.516

Gnomad EAS exome AF: 0.773

Gnomad FIN exome AF: 0.553

Gnomad NFE exome AF: 0.575

Gnomad OTH exome AF: 0.579

GnomAD4 exome AF: 0.573 AC: 827895 AN: 1444486 Hom.: 239000 Cov.: 26 AF XY: 0.572 AC XY: 411791 AN XY: 719720

African (AFR) AF: 0.454 AC: 15020 AN: 33080

American (AMR) AF: 0.610 AC: 27178 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 13488 AN: 26000

East Asian (EAS) AF: 0.748 AC: 29618 AN: 39596

South Asian (SAS) AF: 0.533 AC: 45725 AN: 85806

European-Finnish (FIN) AF: 0.548 AC: 29248 AN: 53348

Middle Eastern (MID) AF: 0.545 AC: 2789 AN: 5122

European-Non Finnish (NFE) AF: 0.575 AC: 630955 AN: 1097284

Other (OTH) AF: 0.568 AC: 33874 AN: 59680

GnomAD4 genome AF: 0.548 AC: 83321 AN: 151916 Hom.: 23231 Cov.: 31 AF XY: 0.553 AC XY: 41038 AN XY: 74236

African (AFR) AF: 0.455 AC: 18833 AN: 41430

American (AMR) AF: 0.598 AC: 9136 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1731 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3901 AN: 5166

South Asian (SAS) AF: 0.533 AC: 2563 AN: 4808

European-Finnish (FIN) AF: 0.554 AC: 5831 AN: 10526

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39418 AN: 67936

Other (OTH) AF: 0.575 AC: 1215 AN: 2112

Alfa AF: 0.568 Hom.: 95272

Bravo AF: 0.548

Asia WGS AF: 0.612 AC: 2129 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (2)
-	-	2	not specified (2)
-	-	1	Limb-Girdle Muscular Dystrophy, Dominant (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.71
PhyloP100		0.54
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.0
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: rs3802100; hg19: chr7-157151234; COSMIC: COSV51096140; COSMIC: COSV51096140;