11-78031780-A-G

Position:

• chr11-78031780-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282406.2(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 NM_001282406.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD14	NM_001282406.2	c.-1+6884T>C		intron_variant			NP_001269335.1
NDUFC2-KCTD14	NM_001203260.2	c.405+6884T>C		intron_variant			NP_001190189.1
NDUFC2-KCTD14	NM_001203261.2	c.311-14510T>C		intron_variant			NP_001190190.1
NDUFC2-KCTD14	NM_001203262.2	c.261+6884T>C		intron_variant			NP_001190191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFC2-KCTD14	ENST00000612612.5	c.405+6884T>C		intron_variant		2		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

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.362

Alfa AF: 0.389 Hom.: 6350

Bravo AF: 0.365

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs2372897; hg19: chr11-77742826;