dbSNP rs375047834: KCNH7:p.Ser1104Ser (chr2-162373482-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_033272.4(KCNH7):c.3312C>T(p.Ser1104Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000597 in 1,539,768 control chromosomes in the GnomAD database, including 1 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 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 1 hom. )

Consequence

KCNH7
NM_033272.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30

Publications

0 publications found

Variant links:

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 links:

GCA (HGNC:15990): (grancalcin) This gene encodes a calcium-binding protein that is abundant in neutrophils and macrophages. In the absence of divalent cation, this protein localizes to the cytosolic fraction; with magnesium alone, it partitions with the granule fraction; and in the presence of magnesium and calcium, it associates with both the granule and membrane fractions. Alternative splicing and use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Aug 2016]

GCA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=1.3 with no splicing effect.

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH7	NM_033272.4 link	c.3312C>T	p.Ser1104Ser	synonymous_variant	Exon 15 of 16	ENST00000332142.10	NP_150375.2	Q9NS40-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH7	ENST00000332142.10 link	c.3312C>T	p.Ser1104Ser	synonymous_variant	Exon 15 of 16	1	NM_033272.4	ENSP00000331727.5		Q9NS40-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000657

AC:

AN:

197960

AF XY:

0.0000188

show subpopulations

Gnomad AFR exome

AF:

0.000896

Gnomad AMR exome

AF:

0.0000388

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000346

AC:

AN:

1387620

Hom.:

Cov.:

AF XY:

0.0000335

AC XY:

AN XY:

686986

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

30494

American (AMR)

AF:

0.0000555

AC:

AN:

36056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23104

East Asian (EAS)

AF:

0.00

AC:

AN:

35874

South Asian (SAS)

AF:

0.00

AC:

AN:

74200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5482

European-Non Finnish (NFE)

AF:

9.32e-7

AC:

AN:

1073534

Other (OTH)

AF:

0.000105

AC:

AN:

57348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000289

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41434

American (AMR)

AF:

0.0000655

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000911

Hom.:

Bravo

AF:

0.000325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.4

(source)

DANN

Benign

0.70

PhyloP100

1.3

Mutation Taster

=96/4

polymorphism

(source)

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

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rs375047834

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over