4-44298231-C-T

Position:

• chr4-44298231-C-T

Variant summary

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

The NM_198353.3(KCTD8):​c.962-122981G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,008 control chromosomes in the GnomAD database, including 33,918 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 0.67 (33918 hom., cov: 31)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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]

LOC107986275 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD8	NM_198353.3	c.962-122981G>A		intron_variant		ENST00000360029.4
LOC107986275	XR_001741677.3	n.5196+837G>A		intron_variant, non_coding_transcript_variant
KCTD8	XM_011513690.4	c.962-4744G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD8	ENST00000360029.4	c.962-122981G>A		intron_variant		1	NM_198353.3	P1
KCTD8	ENST00000515268.1	c.52-4400G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101420 AN: 151890 Hom.: 33884 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.668 AC: 101509 AN: 152008 Hom.: 33918 Cov.: 31 AF XY: 0.666 AC XY: 49454 AN XY: 74296

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.680

Alfa AF: 0.670 Hom.: 69173

Bravo AF: 0.672

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.73
DANN	Benign	0.38

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: rs3963342; hg19: chr4-44300248;