4-44193989-T-C

Position:

• chr4-44193989-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD8	NM_198353.3	c.962-18739A>G		intron_variant		ENST00000360029.4
KCTD8	XM_011513690.4	c.1046-18739A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD8	ENST00000360029.4	c.962-18739A>G		intron_variant		1	NM_198353.3	P1
KCTD8	ENST00000515268.1	c.169-18739A>G		intron_variant		3

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

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.207

Alfa AF: 0.189 Hom.: 3286

Bravo AF: 0.244

Asia WGS AF: 0.262 AC: 909 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.49

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: rs6811002; hg19: chr4-44196006;