rs1859137

Variant names:

• chr16-2700454-A-G
• rs1859137
• NM_018992.4:c.549+538A>G

Variant summary

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

The NM_018992.4(KCTD5):​c.549+538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,084 control chromosomes in the GnomAD database, including 16,284 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 0.45 (16284 hom., cov: 33)
• Consequence: KCTD5 NM_018992.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• Publications: 6 publications found

Genes affected

KCTD5 (HGNC:21423): (potassium channel tetramerization domain containing 5) Enables identical protein binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in cytosol. [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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD5	NM_018992.4	c.549+538A>G		intron_variant	Intron 4 of 5	ENST00000301738.9	NP_061865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD5	ENST00000301738.9	c.549+538A>G		intron_variant	Intron 4 of 5	1	NM_018992.4	ENSP00000301738.4
KCTD5	ENST00000564195.1	c.457+538A>G		intron_variant	Intron 3 of 4	5		ENSP00000456844.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68929 AN: 151966 Hom.: 16265 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.454 AC: 68982 AN: 152084 Hom.: 16284 Cov.: 33 AF XY: 0.449 AC XY: 33397 AN XY: 74330

African (AFR) AF: 0.421 AC: 17439 AN: 41454

American (AMR) AF: 0.414 AC: 6334 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1853 AN: 3470

East Asian (EAS) AF: 0.0895 AC: 462 AN: 5160

South Asian (SAS) AF: 0.345 AC: 1662 AN: 4822

European-Finnish (FIN) AF: 0.535 AC: 5664 AN: 10594

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33941 AN: 67966

Other (OTH) AF: 0.462 AC: 976 AN: 2114

Alfa AF: 0.486 Hom.: 27450

Bravo AF: 0.442

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.54
PhyloP100		-0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1859137; hg19: chr16-2750455;