1-200986864-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001252102.2(KIF21B):c.3669C>T(p.Tyr1223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,613,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: KIF21B NM_001252102.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.139

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 1-200986864-G-A is Benign according to our data. Variant chr1-200986864-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639731.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.139 with no splicing effect.
• BS2: High AC in GnomAd at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF21B	NM_001252102.2	c.3669C>T	p.Tyr1223=	synonymous_variant	26/35	ENST00000461742.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF21B	ENST00000461742.7	c.3669C>T	p.Tyr1223=	synonymous_variant	26/35	1	NM_001252102.2	P3
KIF21B	ENST00000422435.2	c.3669C>T	p.Tyr1223=	synonymous_variant	26/35	1
KIF21B	ENST00000332129.6	c.3669C>T	p.Tyr1223=	synonymous_variant	26/34	1
KIF21B	ENST00000360529.9	c.3669C>T	p.Tyr1223=	synonymous_variant	26/34	1		A2

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152144 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000295 AC: 74 AN: 251078 Hom.: 0 AF XY: 0.000273 AC XY: 37 AN XY: 135674

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000360

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000222 AC: 325 AN: 1461430 Hom.: 0 Cov.: 32 AF XY: 0.000230 AC XY: 167 AN XY: 726952

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.000425

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000441

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.000530

GnomAD4 genome AF: 0.000296 AC: 45 AN: 152262 Hom.: 0 Cov.: 31 AF XY: 0.000296 AC XY: 22 AN XY: 74446

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000223 Hom.: 0

Bravo AF: 0.000317

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

KIF21B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	3.4
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139250432; hg19: chr1-200955992;