1-200991179-G-A

Variant names:

• chr1-200991179-G-A
• rs2297909
• NM_001252102.2:c.2455-30C>T

Variant summary

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

The NM_001252102.2(KIF21B):​c.2455-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,581,260 control chromosomes in the GnomAD database, including 69,180 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 0.27 (5740 hom., cov: 33)
  • Exomes 𝑓: 0.30 (63440 hom.)
• Consequence: KIF21B NM_001252102.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 43 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF21B	NM_001252102.2	MANE Select	c.2455-30C>T		intron	N/A	NP_001239031.1
	KIF21B	NM_001252100.2		c.2455-30C>T		intron	N/A	NP_001239029.1
	KIF21B	NM_017596.4		c.2455-30C>T		intron	N/A	NP_060066.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF21B	ENST00000461742.7	TSL:1 MANE Select	c.2455-30C>T		intron	N/A	ENSP00000433808.1
	KIF21B	ENST00000422435.2	TSL:1	c.2455-30C>T		intron	N/A	ENSP00000411831.2
	KIF21B	ENST00000332129.6	TSL:1	c.2455-30C>T		intron	N/A	ENSP00000328494.2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41021 AN: 151980 Hom.: 5725 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.263

GnomAD2 exomes AF: 0.265 AC: 58105 AN: 219152 AF XY: 0.266

Gnomad AFR exome AF: 0.248

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.219

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.314

Gnomad OTH exome AF: 0.264

GnomAD4 exome AF: 0.295 AC: 421662 AN: 1429162 Hom.: 63440 Cov.: 27 AF XY: 0.292 AC XY: 207821 AN XY: 710998

African (AFR) AF: 0.245 AC: 7986 AN: 32622

American (AMR) AF: 0.192 AC: 8169 AN: 42556

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7028 AN: 25794

East Asian (EAS) AF: 0.213 AC: 8254 AN: 38672

South Asian (SAS) AF: 0.202 AC: 17108 AN: 84718

European-Finnish (FIN) AF: 0.268 AC: 13806 AN: 51558

Middle Eastern (MID) AF: 0.280 AC: 1314 AN: 4698

European-Non Finnish (NFE) AF: 0.313 AC: 341260 AN: 1089414

Other (OTH) AF: 0.283 AC: 16737 AN: 59130

GnomAD4 genome AF: 0.270 AC: 41061 AN: 152098 Hom.: 5740 Cov.: 33 AF XY: 0.266 AC XY: 19782 AN XY: 74366

African (AFR) AF: 0.242 AC: 10037 AN: 41492

American (AMR) AF: 0.213 AC: 3256 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1103 AN: 5164

South Asian (SAS) AF: 0.197 AC: 951 AN: 4830

European-Finnish (FIN) AF: 0.264 AC: 2789 AN: 10582

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20940 AN: 67956

Other (OTH) AF: 0.269 AC: 568 AN: 2112

Alfa AF: 0.294 Hom.: 20514

Bravo AF: 0.267

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.70
DANN	Benign	0.63
PhyloP100		-1.0
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: rs2297909; hg19: chr1-200960307; COSMIC: COSV59753517;