rs1434999

Positions:

• chr2-162770567-C-T

Variant summary

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

The NM_033272.4(KCNH7):​c.307+65970G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,718 control chromosomes in the GnomAD database, including 6,906 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 (6906 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.307+65970G>A		intron_variant		ENST00000332142.10	NP_150375.2
KCNH7-AS1	NR_110258.2	n.54-1364C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH7	ENST00000332142.10	c.307+65970G>A		intron_variant		1	NM_033272.4	ENSP00000331727	P1
KCNH7	ENST00000328032.8	c.307+65970G>A		intron_variant		1		ENSP00000333781
KCNH7-AS1	ENST00000446838.2	n.54-1364C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42446 AN: 151602 Hom.: 6884 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.280 AC: 42503 AN: 151718 Hom.: 6906 Cov.: 32 AF XY: 0.280 AC XY: 20758 AN XY: 74150

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.273

Alfa AF: 0.208 Hom.: 6774

Bravo AF: 0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.85
DANN	Benign	0.75

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: rs1434999; hg19: chr2-163627077;