1-111775862-A-G

Position:

• chr1-111775862-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378969.1(KCND3):​c.*215T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 303,530 control chromosomes in the GnomAD database, including 26,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (10804 hom., cov: 23)
  • Exomes 𝑓: 0.44 (16010 hom.)
• Consequence: KCND3 NM_001378969.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.591

Genes affected

KCND3 (HGNC:6239): (potassium voltage-gated channel subfamily D member 3) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-111775862-A-G is Benign according to our data. Variant chr1-111775862-A-G is described in ClinVar as [Benign]. Clinvar id is 1267630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND3	NM_001378969.1	c.*215T>C		3_prime_UTR_variant	8/8	ENST00000302127.5	NP_001365898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND3	ENST00000302127.5	c.*215T>C		3_prime_UTR_variant	8/8	5	NM_001378969.1	ENSP00000306923	P3
KCND3	ENST00000315987.6	c.*215T>C		3_prime_UTR_variant	8/8	1		ENSP00000319591	P3
KCND3	ENST00000369697.5	c.*215T>C		3_prime_UTR_variant	6/6	1		ENSP00000358711	A1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 54918 AN: 137530 Hom.: 10799 Cov.: 23

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.416

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.438 AC: 72727 AN: 165916 Hom.: 16010 Cov.: 2 AF XY: 0.449 AC XY: 40244 AN XY: 89582

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.693

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.399 AC: 54944 AN: 137614 Hom.: 10804 Cov.: 23 AF XY: 0.414 AC XY: 27370 AN XY: 66150

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.410

Alfa AF: 0.365 Hom.: 3852

Bravo AF: 0.364

Asia WGS AF: 0.609 AC: 2112 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.7
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs12033257; hg19: chr1-112318484;