4-44410920-C-T

Variant names:

• chr4-44410920-C-T
• rs4695718
• NM_198353.3:c.961+36643G>A

Variant summary

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

The NM_198353.3(KCTD8):​c.961+36643G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,024 control chromosomes in the GnomAD database, including 48,460 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 0.79 (48460 hom., cov: 30)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.876 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD8	NM_198353.3	MANE Select	c.961+36643G>A		intron	N/A	NP_938167.1	Q6ZWB6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD8	ENST00000360029.4	TSL:1 MANE Select	c.961+36643G>A		intron	N/A	ENSP00000353129.3	Q6ZWB6
	KCTD8	ENST00000903710.1		c.961+36643G>A		intron	N/A	ENSP00000573769.1
	KCTD8	ENST00000954398.1		c.961+36643G>A		intron	N/A	ENSP00000624457.1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119808 AN: 151906 Hom.: 48428 Cov.: 30

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.789 AC: 119894 AN: 152024 Hom.: 48460 Cov.: 30 AF XY: 0.792 AC XY: 58843 AN XY: 74302

African (AFR) AF: 0.595 AC: 24658 AN: 41420

American (AMR) AF: 0.836 AC: 12764 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2733 AN: 3468

East Asian (EAS) AF: 0.744 AC: 3828 AN: 5142

South Asian (SAS) AF: 0.899 AC: 4328 AN: 4816

European-Finnish (FIN) AF: 0.878 AC: 9292 AN: 10588

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59610 AN: 68002

Other (OTH) AF: 0.788 AC: 1662 AN: 2108

Alfa AF: 0.853 Hom.: 89174

Bravo AF: 0.777

Asia WGS AF: 0.800 AC: 2781 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.058
DANN	Benign	0.76
PhyloP100		-1.7
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: rs4695718; hg19: chr4-44412937;