1-210683243-G-T

Variant names:

• chr1-210683243-G-T
• rs3135473
• NM_172362.3:c.*38C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172362.3(KCNH1):​c.*38C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,582,776 control chromosomes in the GnomAD database, including 398,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41927 hom., cov: 30)
  • Exomes 𝑓: 0.70 (356561 hom.)
• Consequence: KCNH1 NM_172362.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.561

Genes affected

KCNH1 (HGNC:6250): (potassium voltage-gated channel subfamily H member 1) 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 of a voltage-gated non-inactivating delayed rectifier potassium channel. It is activated at the onset of myoblast differentiation. The gene is highly expressed in brain and in myoblasts. Overexpression of the gene may confer a growth advantage to cancer cells and favor tumor cell proliferation. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-210683243-G-T is Benign according to our data. Variant chr1-210683243-G-T is described in ClinVar as [Benign]. Clinvar id is 1276318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH1	NM_172362.3	c.*38C>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000271751.10	NP_758872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH1	ENST00000271751	c.*38C>A		3_prime_UTR_variant	Exon 11 of 11	2	NM_172362.3	ENSP00000271751.4

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111824 AN: 151750 Hom.: 41888 Cov.: 30

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.747

GnomAD2 exomes AF: 0.706 AC: 164345 AN: 232850 AF XY: 0.712

Gnomad AFR exome AF: 0.857

Gnomad AMR exome AF: 0.647

Gnomad ASJ exome AF: 0.802

Gnomad EAS exome AF: 0.649

Gnomad FIN exome AF: 0.594

Gnomad NFE exome AF: 0.698

Gnomad OTH exome AF: 0.723

GnomAD4 exome AF: 0.704 AC: 1006820 AN: 1430908 Hom.: 356561 Cov.: 30 AF XY: 0.707 AC XY: 501759 AN XY: 710022

Gnomad4 AFR exome AF: 0.866 AC: 28142 AN: 32490

Gnomad4 AMR exome AF: 0.654 AC: 27973 AN: 42794

Gnomad4 ASJ exome AF: 0.802 AC: 19903 AN: 24824

Gnomad4 EAS exome AF: 0.644 AC: 25422 AN: 39452

Gnomad4 SAS exome AF: 0.802 AC: 66208 AN: 82592

Gnomad4 FIN exome AF: 0.591 AC: 28901 AN: 48868

Gnomad4 NFE exome AF: 0.697 AC: 763055 AN: 1095100

Gnomad4 Remaining exome AF: 0.719 AC: 42559 AN: 59190

GnomAD4 genome AF: 0.737 AC: 111921 AN: 151868 Hom.: 41927 Cov.: 30 AF XY: 0.735 AC XY: 54557 AN XY: 74212

Gnomad4 AFR AF: 0.854 AC: 0.854087 AN: 0.854087

Gnomad4 AMR AF: 0.715 AC: 0.71494 AN: 0.71494

Gnomad4 ASJ AF: 0.796 AC: 0.795677 AN: 0.795677

Gnomad4 EAS AF: 0.645 AC: 0.644922 AN: 0.644922

Gnomad4 SAS AF: 0.805 AC: 0.80499 AN: 0.80499

Gnomad4 FIN AF: 0.585 AC: 0.58463 AN: 0.58463

Gnomad4 NFE AF: 0.691 AC: 0.691416 AN: 0.691416

Gnomad4 OTH AF: 0.749 AC: 0.749051 AN: 0.749051

Alfa AF: 0.711 Hom.: 22098

Bravo AF: 0.749

Asia WGS AF: 0.751 AC: 2608 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.44
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

Publications

LitVar

Other links and lift over

dbSNP: rs3135473; hg19: chr1-210856585; COSMIC: COSV55073654; COSMIC: COSV55073654;