1-110526711-T-G

Position:

• chr1-110526711-T-G

Variant summary

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

The XR_007066353.1(LOC124904292):​n.312T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,152 control chromosomes in the GnomAD database, including 2,254 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 0.17 (2254 hom., cov: 32)
• Consequence: LOC124904292 XR_007066353.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.38

Genes affected

LOC124904292 (HGNC:):

KCNA2 (HGNC:6220): (potassium voltage-gated channel subfamily A member 2) Potassium 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, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124904292	XR_007066353.1	n.312T>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNA2	ENST00000640680.1	n.2732-4413A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25183 AN: 152034 Hom.: 2251 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.166 AC: 25218 AN: 152152 Hom.: 2254 Cov.: 32 AF XY: 0.164 AC XY: 12164 AN XY: 74394

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0461

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.166

Alfa AF: 0.156 Hom.: 1192

Bravo AF: 0.169

Asia WGS AF: 0.147 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.045
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6700661; hg19: chr1-111069333;