rs543686

chr15-34776108-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_120329.1(GJD2-DT):n.139-1163C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,058 control chromosomes in the GnomAD database, including 9,075 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 0.34 (9075 hom., cov: 33)
• Consequence: GJD2-DT NR_120329.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJD2-DT	NR_120329.1	n.139-1163C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJD2-DT	ENST00000671663.1	n.94+20887C>T		intron_variant, non_coding_transcript_variant
GJD2-DT	ENST00000503496.6	n.139-1163C>T		intron_variant, non_coding_transcript_variant		2
GJD2-DT	ENST00000558707.3	n.119-1163C>T		intron_variant, non_coding_transcript_variant		3
GJD2-DT	ENST00000693120.2	n.117-13699C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51259 AN: 151940 Hom.: 9063 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.337 AC: 51313 AN: 152058 Hom.: 9075 Cov.: 33 AF XY: 0.333 AC XY: 24728 AN XY: 74320

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.308

Alfa AF: 0.341 Hom.: 9295

Bravo AF: 0.328

Asia WGS AF: 0.181 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	7.5
Dann	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs543686; hg19: chr15-35068309;