chr4-44379942-G-T

Position:

• chr4-44379942-G-T

Variant summary

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

The NM_198353.3(KCTD8):​c.961+67621C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 151,796 control chromosomes in the GnomAD database, including 40,808 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 0.73 (40808 hom., cov: 31)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD8	NM_198353.3	c.961+67621C>A		intron_variant		ENST00000360029.4	NP_938167.1
KCTD8	XM_011513690.4	c.961+67621C>A		intron_variant			XP_011511992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD8	ENST00000360029.4	c.961+67621C>A		intron_variant		1	NM_198353.3	ENSP00000353129	P1
KCTD8	ENST00000515268.1	c.51+67621C>A		intron_variant		3		ENSP00000424862

Frequencies

GnomAD3 genomes AF: 0.732 AC: 110975 AN: 151678 Hom.: 40775 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.732 AC: 111064 AN: 151796 Hom.: 40808 Cov.: 31 AF XY: 0.736 AC XY: 54638 AN XY: 74208

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.697

Alfa AF: 0.746 Hom.: 55574

Bravo AF: 0.727

Asia WGS AF: 0.776 AC: 2672 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.50

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: rs4407541; hg19: chr4-44381959;