rs6811002

Variant names:

• chr4-44193989-T-C
• rs6811002
• NM_198353.3:c.962-18739A>G

Variant summary

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

The NM_198353.3(KCTD8):​c.962-18739A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,060 control chromosomes in the GnomAD database, including 5,084 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 0.24 (5084 hom., cov: 32)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD8	NM_198353.3	MANE Select	c.962-18739A>G		intron	N/A	NP_938167.1	Q6ZWB6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD8	ENST00000360029.4	TSL:1 MANE Select	c.962-18739A>G		intron	N/A	ENSP00000353129.3	Q6ZWB6
	KCTD8	ENST00000903710.1		c.1046-18739A>G		intron	N/A	ENSP00000573769.1
	KCTD8	ENST00000954398.1		c.1022-18739A>G		intron	N/A	ENSP00000624457.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36902 AN: 151942 Hom.: 5061 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.243 AC: 36972 AN: 152060 Hom.: 5084 Cov.: 32 AF XY: 0.244 AC XY: 18124 AN XY: 74332

African (AFR) AF: 0.381 AC: 15785 AN: 41476

American (AMR) AF: 0.156 AC: 2388 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1275 AN: 5172

South Asian (SAS) AF: 0.183 AC: 879 AN: 4810

European-Finnish (FIN) AF: 0.245 AC: 2586 AN: 10568

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12948 AN: 67970

Other (OTH) AF: 0.207 AC: 437 AN: 2114

Alfa AF: 0.191 Hom.: 3912

Bravo AF: 0.244

Asia WGS AF: 0.262 AC: 909 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.49
PhyloP100		-0.55
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: rs6811002; hg19: chr4-44196006;