rs12087649

Positions:

• chr1-200982312-T-A
• chr1-200982312-T-C

Variant summary

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

The NM_001252102.2(KIF21B):​c.3842+744A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,034 control chromosomes in the GnomAD database, including 10,049 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 0.32 (10049 hom., cov: 32)
• Consequence: KIF21B NM_001252102.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF21B	NM_001252102.2	c.3842+744A>T		intron_variant		ENST00000461742.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF21B	ENST00000461742.7	c.3842+744A>T		intron_variant		1	NM_001252102.2	P3
KIF21B	ENST00000332129.6	c.3804-1216A>T		intron_variant		1
KIF21B	ENST00000360529.9	c.3804-1216A>T		intron_variant		1		A2
KIF21B	ENST00000422435.2	c.3842+744A>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48133 AN: 151916 Hom.: 10025 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.317 AC: 48201 AN: 152034 Hom.: 10049 Cov.: 32 AF XY: 0.317 AC XY: 23556 AN XY: 74302

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.273

Alfa AF: 0.156 Hom.: 352

Bravo AF: 0.332

Asia WGS AF: 0.336 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.52

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: rs12087649; hg19: chr1-200951440;