chr1-200971052-G-A

Position:

• chr1-200971052-G-A

Variant summary

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

The NM_001252102.2(KIF21B):​c.*2469C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,864 control chromosomes in the GnomAD database, including 6,867 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 0.28 (6841 hom., cov: 34)
  • Exomes 𝑓: 0.31 (26 hom.)
• Consequence: KIF21B NM_001252102.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.*2469C>T		3_prime_UTR_variant	35/35	ENST00000461742.7	NP_001239031.1
KIF21B	NM_001252100.2	c.*3043C>T		3_prime_UTR_variant	35/35		NP_001239029.1
KIF21B	NM_017596.4	c.*3043C>T		3_prime_UTR_variant	34/34		NP_060066.2
KIF21B	NM_001252103.2	c.*2469C>T		3_prime_UTR_variant	34/34		NP_001239032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742	c.*2469C>T		3_prime_UTR_variant	35/35	1	NM_001252102.2	ENSP00000433808.1
KIF21B	ENST00000332129	c.*3043C>T		3_prime_UTR_variant	34/34	1		ENSP00000328494.2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42896 AN: 152120 Hom.: 6830 Cov.: 34

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.305 AC: 191 AN: 626 Hom.: 26 Cov.: 0 AF XY: 0.306 AC XY: 121 AN XY: 396

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.282 AC: 42913 AN: 152238 Hom.: 6841 Cov.: 34 AF XY: 0.288 AC XY: 21412 AN XY: 74422

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.314

Alfa AF: 0.282 Hom.: 2162

Bravo AF: 0.277

Asia WGS AF: 0.310 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3198583; hg19: chr1-200940180; COSMIC: COSV59752148; COSMIC: COSV59752148;