chr4-44274734-T-C

Variant names:

• chr4-44274734-T-C
• rs10007704
• NM_198353.3:c.962-99484A>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.962-99484A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,554 control chromosomes in the GnomAD database, including 11,480 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 0.39 (11480 hom., cov: 31)
• Consequence: KCTD8 NM_198353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 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.962-99484A>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.962-99484A>G		intron	N/A	ENSP00000353129.3
	KCTD8	ENST00000515268.1	TSL:3	c.166+18670A>G		intron	N/A	ENSP00000424862.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58416 AN: 151436 Hom.: 11465 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.386 AC: 58463 AN: 151554 Hom.: 11480 Cov.: 31 AF XY: 0.387 AC XY: 28670 AN XY: 74048

African (AFR) AF: 0.405 AC: 16741 AN: 41372

American (AMR) AF: 0.377 AC: 5709 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1274 AN: 3464

East Asian (EAS) AF: 0.639 AC: 3285 AN: 5138

South Asian (SAS) AF: 0.340 AC: 1640 AN: 4820

European-Finnish (FIN) AF: 0.387 AC: 4079 AN: 10552

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24438 AN: 67754

Other (OTH) AF: 0.396 AC: 832 AN: 2102

Alfa AF: 0.361 Hom.: 15486

Bravo AF: 0.390

Asia WGS AF: 0.543 AC: 1882 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.53
PhyloP100		-0.78
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: rs10007704; hg19: chr4-44276751;