rs2000203

Variant names:

• chr6-72987343-G-A
• rs2000203
• NM_019842.4:c.399-16565G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-72987343-G-A
• chr6-72987343-G-C
• chr6-72987343-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019842.4(KCNQ5):​c.399-16565G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 699,616 control chromosomes in the GnomAD database, including 120,030 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 0.52 (22800 hom., cov: 31)
  • Exomes 𝑓: 0.57 (97230 hom.)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756
• Publications: 6 publications found

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]

KNOP1P4 (HGNC:48922): (lysine rich nucleolar protein 1 pseudogene 4)

LOC105377855 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ5	NM_019842.4	MANE Select	c.399-16565G>A		intron	N/A	NP_062816.2
	KCNQ5	NM_001160133.2		c.399-16565G>A		intron	N/A	NP_001153605.1
	KCNQ5	NM_001160132.2		c.399-16565G>A		intron	N/A	NP_001153604.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ5	ENST00000370398.6	TSL:1 MANE Select	c.399-16565G>A		intron	N/A	ENSP00000359425.1
	KCNQ5	ENST00000629977.2	TSL:1	c.399-16565G>A		intron	N/A	ENSP00000485743.1
	KCNQ5	ENST00000370392.5	TSL:1	c.399-16565G>A		intron	N/A	ENSP00000359419.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78934 AN: 151872 Hom.: 22798 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.571

GnomAD4 exome AF: 0.574 AC: 314365 AN: 547626 Hom.: 97230 Cov.: 3 AF XY: 0.585 AC XY: 175857 AN XY: 300356

African (AFR) AF: 0.215 AC: 3856 AN: 17916

American (AMR) AF: 0.483 AC: 19816 AN: 40986

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 12194 AN: 17190

East Asian (EAS) AF: 0.254 AC: 6972 AN: 27420

South Asian (SAS) AF: 0.631 AC: 43584 AN: 69078

European-Finnish (FIN) AF: 0.582 AC: 26383 AN: 45302

Middle Eastern (MID) AF: 0.651 AC: 1538 AN: 2364

European-Non Finnish (NFE) AF: 0.615 AC: 184406 AN: 300038

Other (OTH) AF: 0.571 AC: 15616 AN: 27332

GnomAD4 genome AF: 0.519 AC: 78948 AN: 151990 Hom.: 22800 Cov.: 31 AF XY: 0.519 AC XY: 38533 AN XY: 74286

African (AFR) AF: 0.273 AC: 11308 AN: 41436

American (AMR) AF: 0.534 AC: 8153 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2549 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1499 AN: 5152

South Asian (SAS) AF: 0.615 AC: 2960 AN: 4816

European-Finnish (FIN) AF: 0.587 AC: 6202 AN: 10566

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.650 AC: 44162 AN: 67958

Other (OTH) AF: 0.572 AC: 1208 AN: 2112

Alfa AF: 0.548 Hom.: 3724

Bravo AF: 0.501

Asia WGS AF: 0.432 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.6
DANN	Uncertain	0.98
PhyloP100		0.76
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: rs2000203; hg19: chr6-73697066; COSMIC: COSV59647904;