chr1-200977234-C-T

Variant names:

• chr1-200977234-C-T
• rs759837389
• NM_001252102.2:c.4303G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001252102.2(KIF21B):​c.4303G>A​(p.Val1435Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000822 in 1,460,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: KIF21B NM_001252102.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252102.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF21B	NM_001252102.2	MANE Select	c.4303G>A	p.Val1435Ile	missense	Exon 31 of 35	NP_001239031.1	O75037-4
	KIF21B	NM_001252100.2		c.4303G>A	p.Val1435Ile	missense	Exon 31 of 35	NP_001239029.1	O75037-1
	KIF21B	NM_017596.4		c.4264G>A	p.Val1422Ile	missense	Exon 30 of 34	NP_060066.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF21B	ENST00000461742.7	TSL:1 MANE Select	c.4303G>A	p.Val1435Ile	missense	Exon 31 of 35	ENSP00000433808.1	O75037-4
	KIF21B	ENST00000422435.2	TSL:1	c.4303G>A	p.Val1435Ile	missense	Exon 31 of 35	ENSP00000411831.2	O75037-1
	KIF21B	ENST00000332129.6	TSL:1	c.4264G>A	p.Val1422Ile	missense	Exon 30 of 34	ENSP00000328494.2	O75037-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250768 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460726 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6 AN XY: 726468

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.0000447 AC: 2 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39648

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111146

Other (OTH) AF: 0.0000166 AC: 1 AN: 60332

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	KIF21B-related Neurodevelopmental disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.8
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.22
Sift	Benign	0.065	T
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.35		Loss of MoRF binding (P = 0.1172)
MVP		0.40
MPC		1.3
ClinPred		0.85	D
GERP RS		4.9
Varity_R		0.11
gMVP		0.18
Mutation Taster		=75/25	polymorphism

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: rs759837389; hg19: chr1-200946362; COSMIC: COSV59759392;