X-48967569-C-T

Position:

• chrX-48967569-C-T

Variant summary

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

The NM_004979.6(KCND1):​c.1122-463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 112,138 control chromosomes in the GnomAD database, including 5,498 homozygotes. There are 9,867 hemizygotes in GnomAD. 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 0.32 (5314 hom., 9658 hem., cov: 21)
  • Exomes 𝑓: 0.36 (184 hom. 209 hem.)
• Consequence: KCND1 NM_004979.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

Genes affected

KCND1 (HGNC:6237): (potassium voltage-gated channel subfamily D member 1) This gene encodes a multipass membrane protein that comprises the pore subunit of the voltage-gated A-type potassium channel, which functions in the repolarization of membrane action potentials. Activity of voltage-gated potassium channels is important in a number of physiological processes, among them the regulation of neurotransmitter release, heart rate, insulin secretion, and smooth muscle contraction. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND1	NM_004979.6	c.1122-463G>A		intron_variant		ENST00000218176.4	NP_004970.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND1	ENST00000218176.4	c.1122-463G>A		intron_variant		1	NM_004979.6	ENSP00000218176.3
KCND1	ENST00000376477.5	c.-473G>A		5_prime_UTR_variant	1/5	2		ENSP00000365660.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 34784 AN: 109137 Hom.: 5314 Cov.: 21 AF XY: 0.307 AC XY: 9647 AN XY: 31437

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.356 AC: 1050 AN: 2946 Hom.: 184 Cov.: 0 AF XY: 0.380 AC XY: 209 AN XY: 550

Gnomad4 AFR exome AF: 0.0411

Gnomad4 AMR exome AF: 0.388

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.282

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.384

GnomAD4 genome AF: 0.319 AC: 34787 AN: 109192 Hom.: 5314 Cov.: 21 AF XY: 0.307 AC XY: 9658 AN XY: 31502

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.368

Alfa AF: 0.401 Hom.: 23608

Bravo AF: 0.315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2064034; hg19: chrX-48823976;