rs2297909

Positions:

• chr1-200991179-G-A
• chr1-200991179-G-T

Variant summary

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

The NM_001252102.2(KIF21B):​c.2455-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,581,260 control chromosomes in the GnomAD database, including 69,180 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 0.27 (5740 hom., cov: 33)
  • Exomes 𝑓: 0.30 (63440 hom.)
• Consequence: KIF21B NM_001252102.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.2455-30C>T		intron_variant		ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7	c.2455-30C>T		intron_variant		1	NM_001252102.2	ENSP00000433808	P3
KIF21B	ENST00000332129.6	c.2455-30C>T		intron_variant		1		ENSP00000328494
KIF21B	ENST00000360529.9	c.2455-30C>T		intron_variant		1		ENSP00000353724	A2
KIF21B	ENST00000422435.2	c.2455-30C>T		intron_variant		1		ENSP00000411831

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41021 AN: 151980 Hom.: 5725 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.263

GnomAD3 exomes AF: 0.265 AC: 58105 AN: 219152 Hom.: 7694 AF XY: 0.266 AC XY: 32098 AN XY: 120712

Gnomad AFR exome AF: 0.248

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.219

Gnomad SAS exome AF: 0.208

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.314

Gnomad OTH exome AF: 0.264

GnomAD4 exome AF: 0.295 AC: 421662 AN: 1429162 Hom.: 63440 Cov.: 27 AF XY: 0.292 AC XY: 207821 AN XY: 710998

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.270 AC: 41061 AN: 152098 Hom.: 5740 Cov.: 33 AF XY: 0.266 AC XY: 19782 AN XY: 74366

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.269

Alfa AF: 0.292 Hom.: 8647

Bravo AF: 0.267

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.70
DANN	Benign	0.63

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: rs2297909; hg19: chr1-200960307; COSMIC: COSV59753517;