rs7689563

chr4-44342924-G-A

Variant summary

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

The NM_198353.3(KCTD8):c.961+104639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,198 control chromosomes in the GnomAD database, including 1,310 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 (1310 hom., cov: 33)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

Genes affected

KCTD8 (HGNC:22394): (potassium channel tetramerization domain containing 8) Predicted to be involved in regulation of G protein-coupled receptor signaling pathway. Predicted to be located in cell projection; postsynaptic membrane; and presynaptic membrane. Predicted to be integral component of membrane. Predicted to be part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD8	NM_198353.3	c.961+104639C>T		intron_variant		ENST00000360029.4
KCTD8	XM_011513690.4	c.962-49437C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD8	ENST00000360029.4	c.961+104639C>T		intron_variant		1	NM_198353.3	P1
KCTD8	ENST00000515268.1	c.52-49093C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18237 AN: 152080 Hom.: 1308 Cov.: 33

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.0750

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.120 AC: 18238 AN: 152198 Hom.: 1310 Cov.: 33 AF XY: 0.122 AC XY: 9044 AN XY: 74386

Gnomad4 AFR AF: 0.0487

Gnomad4 AMR AF: 0.0849

Gnomad4 ASJ AF: 0.0750

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.118

Alfa AF: 0.143 Hom.: 822

Bravo AF: 0.111

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	6.2
Dann	Benign	0.53

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: rs7689563; hg19: chr4-44344941;