Genetic Variant KCND1:c.1122-463G>A (chrX-48967569-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

4 publications found

Variant links:

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]

KCND1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004979.6. 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
	KCND1	NM_004979.6	MANE Select	c.1122-463G>A		intron	N/A	NP_004970.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCND1	ENST00000218176.4	TSL:1 MANE Select	c.1122-463G>A	intron	N/A	ENSP00000218176.3	Q9NSA2-1
KCND1	ENST00000376477.6	TSL:2	c.-473G>A	5_prime_UTR	Exon 1 of 5	ENSP00000365660.1	Q9NSA2-2
KCND1	ENST00000935975.1		c.1122-463G>A	intron	N/A	ENSP00000606034.1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

34784

AN:

109137

Hom.:

5314

Cov.:

show subpopulations

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.:

AF XY:

0.380

AC XY:

209

AN XY:

550

show subpopulations

African (AFR)

AF:

0.0411

AC:

AN:

American (AMR)

AF:

0.388

AC:

216

AN:

556

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

AN:

East Asian (EAS)

AF:

0.163

AC:

AN:

South Asian (SAS)

AF:

0.228

AC:

AN:

167

European-Finnish (FIN)

AF:

0.282

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.381

AC:

705

AN:

1852

Other (OTH)

AF:

0.384

AC:

AN:

138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.319

AC:

34787

AN:

109192

Hom.:

5314

Cov.:

AF XY:

0.307

AC XY:

9658

AN XY:

31502

show subpopulations

African (AFR)

AF:

0.0625

AC:

1892

AN:

30293

American (AMR)

AF:

0.408

AC:

4205

AN:

10317

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

1191

AN:

2593

East Asian (EAS)

AF:

0.257

AC:

882

AN:

3437

South Asian (SAS)

AF:

0.187

AC:

460

AN:

2460

European-Finnish (FIN)

AF:

0.425

AC:

2423

AN:

5701

Middle Eastern (MID)

AF:

0.493

AC:

105

AN:

213

European-Non Finnish (NFE)

AF:

0.441

AC:

22918

AN:

52022

Other (OTH)

AF:

0.368

AC:

544

AN:

1480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

740

1481

2221

2962

3702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.394

Hom.:

30040

Bravo

AF:

0.315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.30

(source)

PhyloP100

-1.2

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over