chr16-84220778-G-A

Variant names:

• chr16-84220778-G-A
• rs39552
• NM_172347.3:c.*1439C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172347.3. 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
	KCNG4	NM_172347.3	MANE Select	c.*1439C>T		3_prime_UTR	Exon 3 of 3	NP_758857.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNG4	ENST00000308251.6	TSL:1 MANE Select	c.*1439C>T		3_prime_UTR	Exon 3 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.750 AC: 6 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.658 AC: 25 AN: 38

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

African (AFR) AF: 0.874 AC: 36314 AN: 41526

American (AMR) AF: 0.675 AC: 10318 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3468

East Asian (EAS) AF: 0.646 AC: 3330 AN: 5152

South Asian (SAS) AF: 0.613 AC: 2961 AN: 4828

European-Finnish (FIN) AF: 0.674 AC: 7130 AN: 10578

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.549 AC: 37286 AN: 67960

Other (OTH) AF: 0.654 AC: 1383 AN: 2116

Alfa AF: 0.593 Hom.: 82763

Bravo AF: 0.672

Asia WGS AF: 0.621 AC: 2160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.29
PhyloP100		-2.4

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

Other links and lift over

dbSNP: rs39552; hg19: chr16-84254384;