1-201005936-G-A

Position:

• chr1-201005936-G-A

Variant summary

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

The NM_001252102.2(KIF21B):​c.448-242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,228 control chromosomes in the GnomAD database, including 5,880 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 (5880 hom., cov: 33)
• Consequence: KIF21B NM_001252102.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF21B	NM_001252102.2	c.448-242C>T		intron_variant		ENST00000461742.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF21B	ENST00000461742.7	c.448-242C>T		intron_variant		1	NM_001252102.2	P3
KIF21B	ENST00000332129.6	c.448-242C>T		intron_variant		1
KIF21B	ENST00000360529.9	c.448-242C>T		intron_variant		1		A2
KIF21B	ENST00000422435.2	c.448-242C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40327 AN: 152110 Hom.: 5869 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.265 AC: 40355 AN: 152228 Hom.: 5880 Cov.: 33 AF XY: 0.260 AC XY: 19371 AN XY: 74408

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.279

Alfa AF: 0.311 Hom.: 8550

Bravo AF: 0.258

Asia WGS AF: 0.235 AC: 819 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	0.59
DANN	Benign	0.40

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: rs10920091; hg19: chr1-200975064;