rs3765023

Positions:

• chr2-162771755-G-A

Variant summary

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

The ENST00000332142.10(KCNH7):​c.307+64782C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,560 control chromosomes in the GnomAD database, including 6,991 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 0.28 (6991 hom., cov: 32)
• Consequence: KCNH7 ENST00000332142.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161

Genes affected

KCNH7 (HGNC:18863): (potassium voltage-gated channel subfamily H member 7) 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. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit. There are at least two alternatively spliced transcript variants derived from this gene and encoding distinct isoforms. [provided by RefSeq, Jul 2008]

KCNH7-AS1 (HGNC:40858): (KCNH7 antisense RNA 1)

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 = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.307+64782C>T		intron_variant		ENST00000332142.10	NP_150375.2
KCNH7-AS1	NR_110258.2	n.54-176G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH7	ENST00000332142.10	c.307+64782C>T		intron_variant		1	NM_033272.4	ENSP00000331727	P1
KCNH7	ENST00000328032.8	c.307+64782C>T		intron_variant		1		ENSP00000333781
KCNH7-AS1	ENST00000446838.2	n.54-176G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42682 AN: 151444 Hom.: 6971 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.282 AC: 42736 AN: 151560 Hom.: 6991 Cov.: 32 AF XY: 0.282 AC XY: 20873 AN XY: 74020

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.275

Alfa AF: 0.222 Hom.: 854

Bravo AF: 0.299

Asia WGS AF: 0.244 AC: 851 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.29

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: rs3765023; hg19: chr2-163628265;