1-62238462-A-G

Position:

• chr1-62238462-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181712.5(KANK4):​c.2884-81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,179,684 control chromosomes in the GnomAD database, including 75,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (9851 hom., cov: 31)
  • Exomes 𝑓: 0.35 (65515 hom.)
• Consequence: KANK4 NM_181712.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.21

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-62238462-A-G is Benign according to our data. Variant chr1-62238462-A-G is described in ClinVar as [Benign]. Clinvar id is 1249680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK4	NM_181712.5	c.2884-81T>C		intron_variant		ENST00000371153.9	NP_859063.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK4	ENST00000371153.9	c.2884-81T>C		intron_variant		1	NM_181712.5	ENSP00000360195.4
KANK4	ENST00000354381.3	c.1000-81T>C		intron_variant		2		ENSP00000346352.3
KANK4	ENST00000371150.5	c.952-81T>C		intron_variant		2		ENSP00000360192.1
KANK4	ENST00000317477.8	c.298-81T>C		intron_variant		2		ENSP00000321161.4

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54103 AN: 151776 Hom.: 9836 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.352 AC: 361301 AN: 1027790 Hom.: 65515 AF XY: 0.349 AC XY: 183124 AN XY: 524970

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.357 AC: 54156 AN: 151894 Hom.: 9851 Cov.: 31 AF XY: 0.356 AC XY: 26434 AN XY: 74240

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.329

Alfa AF: 0.226 Hom.: 521

Bravo AF: 0.350

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41289438; hg19: chr1-62704134;