chr4-44185665-T-C

Variant names:

• chr4-44185665-T-C
• rs4695701
• NM_198353.3:c.962-10415A>G

Variant summary

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

The NM_198353.3(KCTD8):​c.962-10415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,968 control chromosomes in the GnomAD database, including 20,980 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 0.51 (20980 hom., cov: 32)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD8	NM_198353.3	MANE Select	c.962-10415A>G		intron	N/A	NP_938167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD8	ENST00000360029.4	TSL:1 MANE Select	c.962-10415A>G		intron	N/A	ENSP00000353129.3
	KCTD8	ENST00000515268.1	TSL:3	c.167-10415A>G		intron	N/A	ENSP00000424862.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78135 AN: 151852 Hom.: 20943 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.515 AC: 78230 AN: 151968 Hom.: 20980 Cov.: 32 AF XY: 0.512 AC XY: 38060 AN XY: 74284

African (AFR) AF: 0.674 AC: 27953 AN: 41448

American (AMR) AF: 0.446 AC: 6814 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1580 AN: 3470

East Asian (EAS) AF: 0.550 AC: 2829 AN: 5140

South Asian (SAS) AF: 0.529 AC: 2548 AN: 4818

European-Finnish (FIN) AF: 0.397 AC: 4193 AN: 10562

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30556 AN: 67942

Other (OTH) AF: 0.505 AC: 1062 AN: 2104

Alfa AF: 0.471 Hom.: 29065

Bravo AF: 0.526

Asia WGS AF: 0.540 AC: 1878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.83
DANN	Benign	0.56
PhyloP100		-1.5
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: rs4695701; hg19: chr4-44187682;