chr1-201002993-A-T

Variant names:

• chr1-201002993-A-T
• rs756254
• NM_001252102.2:c.1212+593T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001252102.2(KIF21B):​c.1212+593T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0991 in 159,204 control chromosomes in the GnomAD database, including 892 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 0.10 (846 hom., cov: 33)
  • Exomes 𝑓: 0.088 (46 hom.)
• Consequence: KIF21B NM_001252102.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.1212+593T>A		intron_variant	Intron 8 of 34	ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7	c.1212+593T>A		intron_variant	Intron 8 of 34	1	NM_001252102.2	ENSP00000433808.1

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15173 AN: 152146 Hom.: 847 Cov.: 33

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0864

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0951

GnomAD4 exome AF: 0.0882 AC: 612 AN: 6940 Hom.: 46 Cov.: 0 AF XY: 0.0865 AC XY: 307 AN XY: 3550

African (AFR) AF: 0.125 AC: 6 AN: 48

American (AMR) AF: 0.0586 AC: 99 AN: 1688

Ashkenazi Jewish (ASJ) AF: 0.0333 AC: 1 AN: 30

East Asian (EAS) AF: 0.0570 AC: 17 AN: 298

South Asian (SAS) AF: 0.0512 AC: 35 AN: 684

European-Finnish (FIN) AF: 0.181 AC: 13 AN: 72

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.108 AC: 418 AN: 3862

Other (OTH) AF: 0.0927 AC: 23 AN: 248

GnomAD4 genome AF: 0.0996 AC: 15163 AN: 152264 Hom.: 846 Cov.: 33 AF XY: 0.0988 AC XY: 7357 AN XY: 74440

African (AFR) AF: 0.0627 AC: 2608 AN: 41564

American (AMR) AF: 0.0863 AC: 1320 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3470

East Asian (EAS) AF: 0.102 AC: 527 AN: 5176

South Asian (SAS) AF: 0.0637 AC: 307 AN: 4822

European-Finnish (FIN) AF: 0.145 AC: 1532 AN: 10594

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8294 AN: 68020

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.111 Hom.: 112

Bravo AF: 0.0952

Asia WGS AF: 0.0860 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.68
PhyloP100		0.39
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: rs756254; hg19: chr1-200972121;