rs17641529

Variant names:

• chr4-44210148-A-G
• rs17641529
• NM_198353.3:c.962-34898T>C

Variant summary

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

The NM_198353.3(KCTD8):​c.962-34898T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,092 control chromosomes in the GnomAD database, including 4,510 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 (4510 hom., cov: 32)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD8	NM_198353.3	c.962-34898T>C		intron_variant	Intron 1 of 1	ENST00000360029.4	NP_938167.1
KCTD8	XM_011513690.4	c.1046-34898T>C		intron_variant	Intron 2 of 2		XP_011511992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD8	ENST00000360029.4	c.962-34898T>C		intron_variant	Intron 1 of 1	1	NM_198353.3	ENSP00000353129.3
KCTD8	ENST00000515268.1	c.167-34898T>C		intron_variant	Intron 3 of 3	3		ENSP00000424862.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36229 AN: 151972 Hom.: 4503 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.238 AC: 36261 AN: 152092 Hom.: 4510 Cov.: 32 AF XY: 0.240 AC XY: 17850 AN XY: 74342

African (AFR) AF: 0.272 AC: 11284 AN: 41502

American (AMR) AF: 0.244 AC: 3724 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 855 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1549 AN: 5164

South Asian (SAS) AF: 0.330 AC: 1593 AN: 4822

European-Finnish (FIN) AF: 0.209 AC: 2204 AN: 10564

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14392 AN: 67968

Other (OTH) AF: 0.245 AC: 518 AN: 2112

Alfa AF: 0.225 Hom.: 6296

Bravo AF: 0.238

Asia WGS AF: 0.284 AC: 983 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.83
PhyloP100		0.15
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: rs17641529; hg19: chr4-44212165;