rs296565

Variant names:

• chr1-200974929-G-A
• rs296565
• NM_001252102.2:c.4615-16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001252102.2(KIF21B):​c.4615-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,610,992 control chromosomes in the GnomAD database, including 23,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1616 hom., cov: 33)
  • Exomes 𝑓: 0.17 (22371 hom.)
• Consequence: KIF21B NM_001252102.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-200974929-G-A is Benign according to our data. Variant chr1-200974929-G-A is described in ClinVar as Benign. ClinVar VariationId is 1302458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.4615-16C>T		intron_variant	Intron 33 of 34	ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7	c.4615-16C>T		intron_variant	Intron 33 of 34	1	NM_001252102.2	ENSP00000433808.1
KIF21B	ENST00000422435.2	c.4615-16C>T		intron_variant	Intron 33 of 34	1		ENSP00000411831.2
KIF21B	ENST00000332129.6	c.4576-16C>T		intron_variant	Intron 32 of 33	1		ENSP00000328494.2
KIF21B	ENST00000360529.9	c.4576-16C>T		intron_variant	Intron 32 of 33	1		ENSP00000353724.5

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20341 AN: 152094 Hom.: 1615 Cov.: 33

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.147 AC: 36576 AN: 248338 AF XY: 0.152

Gnomad AFR exome AF: 0.0454

Gnomad AMR exome AF: 0.0852

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.118

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.172 AC: 250415 AN: 1458780 Hom.: 22371 Cov.: 34 AF XY: 0.172 AC XY: 124889 AN XY: 725720

African (AFR) AF: 0.0439 AC: 1468 AN: 33438

American (AMR) AF: 0.0902 AC: 4030 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4716 AN: 26116

East Asian (EAS) AF: 0.128 AC: 5094 AN: 39676

South Asian (SAS) AF: 0.147 AC: 12676 AN: 86178

European-Finnish (FIN) AF: 0.144 AC: 7432 AN: 51544

Middle Eastern (MID) AF: 0.198 AC: 1084 AN: 5484

European-Non Finnish (NFE) AF: 0.184 AC: 204025 AN: 1111342

Other (OTH) AF: 0.164 AC: 9890 AN: 60306

GnomAD4 genome AF: 0.134 AC: 20334 AN: 152212 Hom.: 1616 Cov.: 33 AF XY: 0.132 AC XY: 9822 AN XY: 74404

African (AFR) AF: 0.0482 AC: 2003 AN: 41544

American (AMR) AF: 0.133 AC: 2032 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3464

East Asian (EAS) AF: 0.119 AC: 612 AN: 5160

South Asian (SAS) AF: 0.146 AC: 703 AN: 4830

European-Finnish (FIN) AF: 0.149 AC: 1575 AN: 10594

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12193 AN: 67998

Other (OTH) AF: 0.145 AC: 307 AN: 2114

Alfa AF: 0.153 Hom.: 735

Bravo AF: 0.128

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.63
PhyloP100		-0.28
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: rs296565; hg19: chr1-200944057; COSMIC: COSV59759157;