Variant rs187401737 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000374403.4(KIF4A):c.2118+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,144,802 control chromosomes in the GnomAD database, including 5 homozygotes. There are 1,124 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., 47 hem., cov: 22)

Exomes 𝑓: 0.0035 ( 5 hom. 1077 hem. )

Consequence

KIF4A
ENST00000374403.4 splice_region, intron

Scores

Splicing: ADA: 0.0001412

Clinical Significance

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

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

KIF4A (HGNC:13339): (kinesin family member 4A) This gene encodes a member of the kinesin 4 subfamily of kinesin related proteins. The encoded protein is an ATP dependent microtubule-based motor protein that is involved in the intracellular transport of membranous organelles. This protein also associates with condensed chromosome arms and may be involved in maintaining chromosome integrity during mitosis. This protein may also be involved in the organization of the central spindle prior to cytokinesis. A pseudogene of this gene is found on chromosome X.[provided by RefSeq, Mar 2010]

KIF4A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant X-70386708-A-G is Benign according to our data. Variant chrX-70386708-A-G is described in ClinVar as [Benign]. Clinvar id is 435643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-70386708-A-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 47 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF4A	NM_012310.5 linkuse as main transcript	c.2118+7A>G		splice_region_variant, intron_variant		ENST00000374403.4	NP_036442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF4A	ENST00000374403.4 linkuse as main transcript	c.2118+7A>G		splice_region_variant, intron_variant		1	NM_012310.5	ENSP00000363524	P1	O95239-1

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

230

AN:

112021

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

AN XY:

34169

show subpopulations

Gnomad AFR

AF:

0.000454

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000818

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00372

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.00193

AC:

352

AN:

182475

Hom.:

AF XY:

0.00179

AC XY:

120

AN XY:

66969

show subpopulations

Gnomad AFR exome

AF:

0.000457

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00100

Gnomad NFE exome

AF:

0.00331

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00346

AC:

3571

AN:

1032727

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

1077

AN XY:

307167

show subpopulations

Gnomad4 AFR exome

AF:

0.000317

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.0000528

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000938

Gnomad4 NFE exome

AF:

0.00424

Gnomad4 OTH exome

AF:

0.00321

GnomAD4 genome

AF:

0.00205

AC:

230

AN:

112075

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

AN XY:

34233

show subpopulations

Gnomad4 AFR

AF:

0.000453

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000818

Gnomad4 NFE

AF:

0.00372

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.00204

Hom.:

Bravo

AF:

0.00246

EpiCase

AF:

0.00409

EpiControl

AF:

0.00390

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 05, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.9

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over