rs7196274

Positions:

• chr16-84228503-G-A
• chr16-84228503-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.757-5483C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,960 control chromosomes in the GnomAD database, including 5,243 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 0.26 (5243 hom., cov: 32)
• Consequence: KCNG4 NM_172347.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNG4	NM_172347.3	c.757-5483C>T		intron_variant		ENST00000308251.6	NP_758857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNG4	ENST00000308251.6	c.757-5483C>T		intron_variant		1	NM_172347.3	ENSP00000312129.4

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39211 AN: 151844 Hom.: 5231 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.151

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.258 AC: 39245 AN: 151960 Hom.: 5243 Cov.: 32 AF XY: 0.251 AC XY: 18630 AN XY: 74272

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.232

Alfa AF: 0.258 Hom.: 10541

Bravo AF: 0.270

Asia WGS AF: 0.256 AC: 891 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.26

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

LitVar

Other links and lift over

dbSNP: rs7196274; hg19: chr16-84262109;