rs10494828

Variant names:

• chr1-200987904-G-A
• rs10494828
• NM_001252102.2:c.3408+392C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001252102.2(KIF21B):​c.3408+392C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,148 control chromosomes in the GnomAD database, including 4,061 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 0.22 (4061 hom., cov: 32)
• Consequence: KIF21B NM_001252102.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.3408+392C>T		intron_variant	Intron 24 of 34	ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7	c.3408+392C>T		intron_variant	Intron 24 of 34	1	NM_001252102.2	ENSP00000433808.1
KIF21B	ENST00000422435.2	c.3408+392C>T		intron_variant	Intron 24 of 34	1		ENSP00000411831.2
KIF21B	ENST00000332129.6	c.3408+392C>T		intron_variant	Intron 24 of 33	1		ENSP00000328494.2
KIF21B	ENST00000360529.9	c.3408+392C>T		intron_variant	Intron 24 of 33	1		ENSP00000353724.5

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33353 AN: 152030 Hom.: 4059 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.219 AC: 33357 AN: 152148 Hom.: 4061 Cov.: 32 AF XY: 0.212 AC XY: 15779 AN XY: 74372

African (AFR) AF: 0.173 AC: 7166 AN: 41494

American (AMR) AF: 0.163 AC: 2487 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3470

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5186

South Asian (SAS) AF: 0.107 AC: 518 AN: 4824

European-Finnish (FIN) AF: 0.204 AC: 2166 AN: 10602

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19337 AN: 67976

Other (OTH) AF: 0.206 AC: 435 AN: 2110

Alfa AF: 0.256 Hom.: 6729

Bravo AF: 0.216

Asia WGS AF: 0.0660 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.38
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10494828; hg19: chr1-200957032;