Genetic Variant KIF21B:c.4615-16C>T (chr1-200974929-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001252102.2(KIF21B):c.4615-16C>T variant causes a 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
NM_001252102.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.279

Publications

14 publications found

Variant links:

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]

KIF21B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF21B	NM_001252102.2	MANE Select	c.4615-16C>T	intron	N/A	NP_001239031.1	O75037-4
KIF21B	NM_001252100.2		c.4615-16C>T	intron	N/A	NP_001239029.1	O75037-1
KIF21B	NM_017596.4		c.4576-16C>T	intron	N/A	NP_060066.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF21B	ENST00000461742.7	TSL:1 MANE Select	c.4615-16C>T	intron	N/A	ENSP00000433808.1	O75037-4
KIF21B	ENST00000422435.2	TSL:1	c.4615-16C>T	intron	N/A	ENSP00000411831.2	O75037-1
KIF21B	ENST00000332129.6	TSL:1	c.4576-16C>T	intron	N/A	ENSP00000328494.2	O75037-2

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20341

AN:

152094

Hom.:

1615

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.147

AC:

36576

AN:

248338

AF XY:

0.152

show subpopulations

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 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.:

AF XY:

0.172

AC XY:

124889

AN XY:

725720

show subpopulations

African (AFR)

AF:

0.0439

AC:

1468

AN:

33438

American (AMR)

AF:

0.0902

AC:

4030

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

4716

AN:

26116

East Asian (EAS)

AF:

0.128

AC:

5094

AN:

39676

South Asian (SAS)

AF:

0.147

AC:

12676

AN:

86178

European-Finnish (FIN)

AF:

0.144

AC:

7432

AN:

51544

Middle Eastern (MID)

AF:

0.198

AC:

1084

AN:

5484

European-Non Finnish (NFE)

AF:

0.184

AC:

204025

AN:

1111342

Other (OTH)

AF:

0.164

AC:

9890

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

11859

23718

35578

47437

59296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7012

14024

21036

28048

35060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.134

AC:

20334

AN:

152212

Hom.:

1616

Cov.:

AF XY:

0.132

AC XY:

9822

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0482

AC:

2003

AN:

41544

American (AMR)

AF:

0.133

AC:

2032

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

659

AN:

3464

East Asian (EAS)

AF:

0.119

AC:

612

AN:

5160

South Asian (SAS)

AF:

0.146

AC:

703

AN:

4830

European-Finnish (FIN)

AF:

0.149

AC:

1575

AN:

10594

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.179

AC:

12193

AN:

67998

Other (OTH)

AF:

0.145

AC:

307

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

923

1846

2770

3693

4616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.153

Hom.:

735

Bravo

AF:

0.128

Asia WGS

AF:

0.117

AC:

407

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.1

(source)

DANN

Benign

0.63

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over