rs12089839

Positions:

• chr1-200997894-G-A
• chr1-200997894-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.2077+490C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 152,218 control chromosomes in the GnomAD database, including 297 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 0.043 (297 hom., cov: 33)
• Consequence: KIF21B NM_001252102.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.2077+490C>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.2077+490C>T		intron_variant		1	NM_001252102.2	ENSP00000433808	P3
KIF21B	ENST00000332129.6	c.2077+490C>T		intron_variant		1		ENSP00000328494
KIF21B	ENST00000360529.9	c.2077+490C>T		intron_variant		1		ENSP00000353724	A2
KIF21B	ENST00000422435.2	c.2077+490C>T		intron_variant		1		ENSP00000411831

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6556 AN: 152100 Hom.: 294 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0245

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.0292

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

GnomAD4 genome AF: 0.0433 AC: 6587 AN: 152218 Hom.: 297 Cov.: 33 AF XY: 0.0460 AC XY: 3426 AN XY: 74440

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0574

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0692

Gnomad4 FIN AF: 0.0245

Gnomad4 NFE AF: 0.00295

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0104 Hom.: 67

Bravo AF: 0.0492

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.77

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: rs12089839; hg19: chr1-200967022;