rs187401737

Variant names:

• chrX-70386708-A-G
• rs187401737
• NM_012310.5:c.2118+7A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_012310.5(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 NM_012310.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001412
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.60
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 100

  Inheritance: Unknown, XL Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.
• BS2: High Hemizygotes in GnomAd4 at 47 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF4A	NM_012310.5	c.2118+7A>G		splice_region_variant, intron_variant	Intron 19 of 30	ENST00000374403.4	NP_036442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF4A	ENST00000374403.4	c.2118+7A>G		splice_region_variant, intron_variant	Intron 19 of 30	1	NM_012310.5	ENSP00000363524.3

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 230 AN: 112021 Hom.: 0 Cov.: 22

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

GnomAD2 exomes AF: 0.00193 AC: 352 AN: 182475 AF XY: 0.00179

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 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.: 5 Cov.: 24 AF XY: 0.00351 AC XY: 1077 AN XY: 307167

African (AFR) AF: 0.000317 AC: 8 AN: 25204

American (AMR) AF: 0.00182 AC: 64 AN: 35137

Ashkenazi Jewish (ASJ) AF: 0.0000528 AC: 1 AN: 18951

East Asian (EAS) AF: 0.00 AC: 0 AN: 29950

South Asian (SAS) AF: 0.00 AC: 0 AN: 52542

European-Finnish (FIN) AF: 0.000938 AC: 38 AN: 40494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3950

European-Non Finnish (NFE) AF: 0.00424 AC: 3319 AN: 782558

Other (OTH) AF: 0.00321 AC: 141 AN: 43941

GnomAD4 genome AF: 0.00205 AC: 230 AN: 112075 Hom.: 0 Cov.: 22 AF XY: 0.00137 AC XY: 47 AN XY: 34233

African (AFR) AF: 0.000453 AC: 14 AN: 30899

American (AMR) AF: 0.00105 AC: 11 AN: 10490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2681

European-Finnish (FIN) AF: 0.000818 AC: 5 AN: 6111

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00372 AC: 198 AN: 53237

Other (OTH) AF: 0.00131 AC: 2 AN: 1531

Alfa AF: 0.00204 Hom.: 11

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

Submissions by phenotype

not specified Benign:1

Aug 05, 2016

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.9
DANN	Benign	0.89
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs187401737; hg19: chrX-69606558;