rs39552

Positions:

• chr16-84220778-G-A
• chr16-84220778-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172347.3(KCNG4):​c.*1439C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,160 control chromosomes in the GnomAD database, including 35,109 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 0.66 (35095 hom., cov: 32)
  • Exomes 𝑓: 0.71 (14 hom.)
• Consequence: KCNG4 NM_172347.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

Genes affected

KCNG4 (HGNC:19697): (potassium voltage-gated channel modifier subfamily G member 4) 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 G. This member functions as a modulatory subunit. The gene has strong expression in brain. Multiple alternatively spliced variants have been found in normal and cancerous tissues. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNG4	NM_172347.3	c.*1439C>T		3_prime_UTR_variant	3/3	ENST00000308251.6	NP_758857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNG4	ENST00000308251	c.*1439C>T		3_prime_UTR_variant	3/3	1	NM_172347.3	ENSP00000312129.4

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101013 AN: 151990 Hom.: 35041 Cov.: 32

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.652

GnomAD4 exome AF: 0.712 AC: 37 AN: 52 Hom.: 14 Cov.: 0 AF XY: 0.727 AC XY: 32 AN XY: 44

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.658

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.665 AC: 101131 AN: 152108 Hom.: 35095 Cov.: 32 AF XY: 0.669 AC XY: 49730 AN XY: 74344

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.654

Alfa AF: 0.571 Hom.: 43574

Bravo AF: 0.672

Asia WGS AF: 0.621 AC: 2160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs39552; hg19: chr16-84254384;