rs1434999

Variant names:

• chr2-162770567-C-T
• rs1434999
• NM_033272.4:c.307+65970G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.307+65970G>A		intron_variant	Intron 2 of 15	ENST00000332142.10	NP_150375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH7	ENST00000332142.10	c.307+65970G>A		intron_variant	Intron 2 of 15	1	NM_033272.4	ENSP00000331727.5
KCNH7	ENST00000328032.8	c.307+65970G>A		intron_variant	Intron 2 of 7	1		ENSP00000333781.4
KCNH7-AS1	ENST00000446838.2	n.54-1364C>T		intron_variant	Intron 1 of 4	1
KCNH7-AS1	ENST00000780946.1	n.175-1364C>T		intron_variant	Intron 1 of 4

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

African (AFR) AF: 0.454 AC: 18797 AN: 41378

American (AMR) AF: 0.278 AC: 4226 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1580 AN: 5164

South Asian (SAS) AF: 0.146 AC: 706 AN: 4828

European-Finnish (FIN) AF: 0.226 AC: 2372 AN: 10514

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.194 AC: 13139 AN: 67842

Other (OTH) AF: 0.273 AC: 574 AN: 2100

Alfa AF: 0.222 Hom.: 16941

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
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1434999; hg19: chr2-163627077;