1-200974929-G-A

Position:

• chr1-200974929-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000461742.7(KIF21B):​c.4615-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,610,992 control chromosomes in the GnomAD database, including 23,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1616 hom., cov: 33)
  • Exomes 𝑓: 0.17 (22371 hom.)
• Consequence: KIF21B ENST00000461742.7 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-200974929-G-A is Benign according to our data. Variant chr1-200974929-G-A is described in ClinVar as [Benign]. Clinvar id is 1302458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.4615-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7	c.4615-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001252102.2	ENSP00000433808	P3
KIF21B	ENST00000332129.6	c.4576-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000328494
KIF21B	ENST00000360529.9	c.4576-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000353724	A2
KIF21B	ENST00000422435.2	c.4615-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000411831

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20341 AN: 152094 Hom.: 1615 Cov.: 33

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.146

GnomAD3 exomes AF: 0.147 AC: 36576 AN: 248338 Hom.: 2979 AF XY: 0.152 AC XY: 20463 AN XY: 134338

Gnomad AFR exome AF: 0.0454

Gnomad AMR exome AF: 0.0852

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.118

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.172 AC: 250415 AN: 1458780 Hom.: 22371 Cov.: 34 AF XY: 0.172 AC XY: 124889 AN XY: 725720

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.0902

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.134 AC: 20334 AN: 152212 Hom.: 1616 Cov.: 33 AF XY: 0.132 AC XY: 9822 AN XY: 74404

Gnomad4 AFR AF: 0.0482

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.145

Alfa AF: 0.146 Hom.: 429

Bravo AF: 0.128

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.63

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: rs296565; hg19: chr1-200944057; COSMIC: COSV59759157;