chr11-78031780-A-G

Variant names:

• chr11-78031780-A-G
• rs2372897
• ENST00000533144.1:c.-1+6884T>C

Variant summary

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

The ENST00000533144.1(KCTD14):​c.-1+6884T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,074 control chromosomes in the GnomAD database, including 10,612 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 0.37 (10612 hom., cov: 32)
• Consequence: KCTD14 ENST00000533144.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• Publications: 9 publications found

Genes affected

KCTD14 (HGNC:23295): (potassium channel tetramerization domain containing 14) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

NDUFC2-KCTD14 (HGNC:42956): (NDUFC2-KCTD14 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NDUFC2 (NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2, 14.5kDa) and KCTD14 (potassium channel tetramerisation domain containing 14) genes on chromosome 11. The read-through transcripts share sequence identity with the upstream gene product and one variant has a frameshifted C-terminal region derived from the downstream gene exons. [provided by RefSeq, Feb 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000533144.1. 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
	KCTD14	NM_001282406.2		c.-1+6884T>C		intron	N/A	NP_001269335.1
	NDUFC2-KCTD14	NM_001203260.2		c.405+6884T>C		intron	N/A	NP_001190189.1
	NDUFC2-KCTD14	NM_001203261.2		c.311-14510T>C		intron	N/A	NP_001190190.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD14	ENST00000533144.1	TSL:1	c.-1+6884T>C		intron	N/A	ENSP00000431155.1
	NDUFC2-KCTD14	ENST00000530054.1	TSL:2	c.311-14510T>C		intron	N/A	ENSP00000432614.1
	NDUFC2-KCTD14	ENST00000612612.5	TSL:2	c.405+6884T>C		intron	N/A	ENSP00000478766.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55925 AN: 151956 Hom.: 10608 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.368 AC: 55945 AN: 152074 Hom.: 10612 Cov.: 32 AF XY: 0.371 AC XY: 27595 AN XY: 74332

African (AFR) AF: 0.275 AC: 11425 AN: 41484

American (AMR) AF: 0.470 AC: 7184 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1382 AN: 5162

South Asian (SAS) AF: 0.362 AC: 1747 AN: 4822

European-Finnish (FIN) AF: 0.440 AC: 4659 AN: 10578

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26701 AN: 67978

Other (OTH) AF: 0.362 AC: 763 AN: 2108

Alfa AF: 0.384 Hom.: 8739

Bravo AF: 0.365

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.91
PhyloP100		0.39
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: rs2372897; hg19: chr11-77742826;