rs7682929

Variant names:

• chr4-44295892-C-A
• rs7682929
• NM_198353.3:c.962-120642G>T

Variant summary

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

The NM_198353.3(KCTD8):​c.962-120642G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0518 in 152,228 control chromosomes in the GnomAD database, including 272 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 0.052 (272 hom., cov: 32)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• 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]

LOC107986275 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD8	NM_198353.3	c.962-120642G>T		intron_variant	Intron 1 of 1	ENST00000360029.4	NP_938167.1
KCTD8	XM_011513690.4	c.962-2405G>T		intron_variant	Intron 1 of 2		XP_011511992.1
LOC107986275	XR_001741677.3	n.5197-2061G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD8	ENST00000360029.4	c.962-120642G>T		intron_variant	Intron 1 of 1	1	NM_198353.3	ENSP00000353129.3
KCTD8	ENST00000515268.1	c.50-2061G>T		intron_variant	Intron 1 of 3	3		ENSP00000424862.1

Frequencies

GnomAD3 genomes AF: 0.0518 AC: 7885 AN: 152110 Hom.: 272 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0482

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0613

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0560

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

GnomAD4 genome AF: 0.0518 AC: 7882 AN: 152228 Hom.: 272 Cov.: 32 AF XY: 0.0491 AC XY: 3658 AN XY: 74428

African (AFR) AF: 0.0141 AC: 586 AN: 41536

American (AMR) AF: 0.0481 AC: 736 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 122 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4832

European-Finnish (FIN) AF: 0.0613 AC: 650 AN: 10596

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5515 AN: 68002

Other (OTH) AF: 0.0555 AC: 117 AN: 2110

Alfa AF: 0.0692 Hom.: 354

Bravo AF: 0.0496

Asia WGS AF: 0.00982 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.26
PhyloP100		-0.63
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: rs7682929; hg19: chr4-44297909;