dbSNP rs2796051: KCNQ5:c.1468+2511G>A (chr6-73136152-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019842.4(KCNQ5):c.1468+2511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,072 control chromosomes in the GnomAD database, including 2,356 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 0.12 ( 2356 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

KCNQ5
NM_019842.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.288

Publications

3 publications found

Variant links:

Genes affected

KCNQ5 (HGNC:6299): (potassium voltage-gated channel subfamily Q member 5) This gene is a member of the KCNQ potassium channel gene family that is differentially expressed in subregions of the brain and in skeletal muscle. The protein encoded by this gene yields currents that activate slowly with depolarization and can form heteromeric channels with the protein encoded by the KCNQ3 gene. Currents expressed from this protein have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic receptor activation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

KCNQ5 links:

KCNQ5-AS1 (HGNC:40323): (KCNQ5 antisense RNA 1)

KCNQ5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019842.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCNQ5	NM_019842.4	MANE Select	c.1468+2511G>A	intron	N/A	NP_062816.2
KCNQ5-AS1	NR_046621.1		n.225C>T	non_coding_transcript_exon	Exon 3 of 5
KCNQ5	NM_001160133.2		c.1525+2511G>A	intron	N/A	NP_001153605.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCNQ5	ENST00000370398.6	TSL:1 MANE Select	c.1468+2511G>A	intron	N/A	ENSP00000359425.1
KCNQ5	ENST00000629977.2	TSL:1	c.1441+2511G>A	intron	N/A	ENSP00000485743.1
KCNQ5-AS1	ENST00000429832.1	TSL:5	n.225C>T	non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18864

AN:

151946

Hom.:

2358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0636

Gnomad ASJ

AF:

0.0902

Gnomad EAS

AF:

0.0547

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.0351

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0416

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.124

AC:

18892

AN:

152064

Hom.:

2356

Cov.:

AF XY:

0.120

AC XY:

8908

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.331

AC:

13726

AN:

41416

American (AMR)

AF:

0.0635

AC:

970

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0902

AC:

313

AN:

3470

East Asian (EAS)

AF:

0.0548

AC:

284

AN:

5178

South Asian (SAS)

AF:

0.0291

AC:

140

AN:

4818

European-Finnish (FIN)

AF:

0.0351

AC:

372

AN:

10584

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0416

AC:

2829

AN:

68008

Other (OTH)

AF:

0.104

AC:

218

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

700

1401

2101

2802

3502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0680

Hom.:

1053

Bravo

AF:

0.136

Asia WGS

AF:

0.0640

AC:

223

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.3

(source)

DANN

Benign

0.56

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over