rs533021

Variant names:

• chr15-34788730-T-C
• rs533021
• ENST00000503496.6:n.299+11299T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-34788730-T-C
• chr15-34788730-T-A

Variant summary

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

The ENST00000503496.6(GJD2-DT):​n.299+11299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,060 control chromosomes in the GnomAD database, including 24,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24431 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GJD2-DT ENST00000503496.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.167
• Publications: 18 publications found

Genes affected

GJD2-DT (HGNC:55560): (GJD2 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-34788730-T-C is Benign according to our data. Variant chr15-34788730-T-C is described in ClinVar as Benign. ClinVar VariationId is 315653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000503496.6. 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
	GJD2-DT	NR_120329.1		n.299+11299T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJD2-DT	ENST00000503496.6	TSL:2	n.299+11299T>C		intron	N/A
	GJD2-DT	ENST00000558707.4	TSL:3	n.322-1077T>C		intron	N/A
	GJD2-DT	ENST00000671663.2		n.139-21766T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83756 AN: 151942 Hom.: 24430 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.566

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.551 AC: 83785 AN: 152060 Hom.: 24431 Cov.: 32 AF XY: 0.551 AC XY: 40919 AN XY: 74318

African (AFR) AF: 0.374 AC: 15494 AN: 41454

American (AMR) AF: 0.498 AC: 7603 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2375 AN: 3466

East Asian (EAS) AF: 0.371 AC: 1917 AN: 5172

South Asian (SAS) AF: 0.533 AC: 2567 AN: 4818

European-Finnish (FIN) AF: 0.693 AC: 7327 AN: 10578

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44454 AN: 67978

Other (OTH) AF: 0.564 AC: 1192 AN: 2112

Alfa AF: 0.609 Hom.: 68622

Bravo AF: 0.527

Asia WGS AF: 0.437 AC: 1523 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Dilated cardiomyopathy 1R (1)
-	-	1	Hypertrophic cardiomyopathy 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.68
PhyloP100		0.17
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: rs533021; hg19: chr15-35080931;