1-200976808-C-G

Variant names:

• chr1-200976808-C-G
• rs142799216
• NM_001252102.2:c.4411G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001252102.2(KIF21B):​c.4411G>C​(p.Val1471Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,186 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1471M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KIF21B NM_001252102.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.4411G>C	p.Val1471Leu	missense	Exon 32 of 35	NP_001239031.1	O75037-4
	KIF21B	NM_001252100.2		c.4411G>C	p.Val1471Leu	missense	Exon 32 of 35	NP_001239029.1	O75037-1
	KIF21B	NM_017596.4		c.4372G>C	p.Val1458Leu	missense	Exon 31 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.4411G>C	p.Val1471Leu	missense	Exon 32 of 35	ENSP00000433808.1	O75037-4
	KIF21B	ENST00000422435.2	TSL:1	c.4411G>C	p.Val1471Leu	missense	Exon 32 of 35	ENSP00000411831.2	O75037-1
	KIF21B	ENST00000332129.6	TSL:1	c.4372G>C	p.Val1458Leu	missense	Exon 31 of 34	ENSP00000328494.2	O75037-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461186 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726836

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111546

Other (OTH) AF: 0.0000166 AC: 1 AN: 60364

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Uncertain	0.011	D
Sift4G	Benign	0.091	T
Polyphen		0.99	D
Vest4		0.73
MutPred		0.53		Gain of relative solvent accessibility (P = 0.0522)
MVP		0.59
MPC		1.4
ClinPred		0.94	D
GERP RS		4.9
Varity_R		0.27
gMVP		0.37
Mutation Taster		=80/20	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: rs142799216; hg19: chr1-200945936;