rs958802

Positions:

• chr1-62257894-C-T

Variant summary

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

The NM_181712.5(KANK4):​c.2540-4685G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,132 control chromosomes in the GnomAD database, including 7,661 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 0.29 (7661 hom., cov: 32)
• Consequence: KANK4 NM_181712.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201

Genes affected

KANK4 (HGNC:27263): (KN motif and ankyrin repeat domains 4) Predicted to be involved in negative regulation of actin filament polymerization. Located in cytosol and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK4	NM_181712.5	c.2540-4685G>A		intron_variant		ENST00000371153.9	NP_859063.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK4	ENST00000371153.9	c.2540-4685G>A		intron_variant		1	NM_181712.5	ENSP00000360195.4
KANK4	ENST00000354381.3	c.656-4685G>A		intron_variant		2		ENSP00000346352.3
KANK4	ENST00000371150.5	c.608-4685G>A		intron_variant		2		ENSP00000360192.1
KANK4	ENST00000317477.8	c.-47-4685G>A		intron_variant		2		ENSP00000321161.4

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43750 AN: 152012 Hom.: 7661 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.288 AC: 43749 AN: 152132 Hom.: 7661 Cov.: 32 AF XY: 0.289 AC XY: 21511 AN XY: 74358

Gnomad4 AFR AF: 0.0930

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.295

Alfa AF: 0.371 Hom.: 14288

Bravo AF: 0.271

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.1
DANN	Benign	0.74

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: rs958802; hg19: chr1-62723566;