1-201002993-A-T

Position:

• chr1-201002993-A-T

Variant summary

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

The NM_001252102.2(KIF21B):​c.1212+593T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0991 in 159,204 control chromosomes in the GnomAD database, including 892 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 0.10 (846 hom., cov: 33)
  • Exomes 𝑓: 0.088 (46 hom.)
• Consequence: KIF21B NM_001252102.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

Genes affected

KIF21B (HGNC:29442): (kinesin family member 21B) This gene encodes a member of the kinesin superfamily. Kinesins are ATP-dependent microtubule-based motor proteins that are involved in the intracellular transport of membranous organelles. Single nucleotide polymorphisms in this gene are associated with inflammatory bowel disease and multiple sclerosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

KIF21B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.1212+593T>A		intron_variant		ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7	c.1212+593T>A		intron_variant		1	NM_001252102.2	ENSP00000433808.1

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15173 AN: 152146 Hom.: 847 Cov.: 33

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0864

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0951

GnomAD4 exome AF: 0.0882 AC: 612 AN: 6940 Hom.: 46 Cov.: 0 AF XY: 0.0865 AC XY: 307 AN XY: 3550

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.0586

Gnomad4 ASJ exome AF: 0.0333

Gnomad4 EAS exome AF: 0.0570

Gnomad4 SAS exome AF: 0.0512

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0927

GnomAD4 genome AF: 0.0996 AC: 15163 AN: 152264 Hom.: 846 Cov.: 33 AF XY: 0.0988 AC XY: 7357 AN XY: 74440

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.0863

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0637

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0937

Alfa AF: 0.111 Hom.: 112

Bravo AF: 0.0952

Asia WGS AF: 0.0860 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.68

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: rs756254; hg19: chr1-200972121;