Variant 17-74342626-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153209.4(KIF19):c.232-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,609,608 control chromosomes in the GnomAD database, including 58,938 homozygotes. 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 0.23 ( 4715 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54223 hom. )

Consequence

KIF19
NM_153209.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002592

Clinical Significance

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

Conservation

PhyloP100: 0.0720

Variant links:

Genes affected

KIF19 (HGNC:26735): (kinesin family member 19) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in axonemal microtubule depolymerization; microtubule-based movement; and plus-end specific microtubule depolymerization. Predicted to be located in cilium. Predicted to be part of kinesin complex. Predicted to be active in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

KIF19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-74342626-G-A is Benign according to our data. Variant chr17-74342626-G-A is described in ClinVar as [Benign]. Clinvar id is 1287685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF19	NM_153209.4 linkuse as main transcript	c.232-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000389916.5	NP_694941.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
KIF19	ENST00000389916.5 linkuse as main transcript	c.232-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_153209.4	ENSP00000374566	P1	Q2TAC6-1
KIF19	ENST00000359939.10 linkuse as main transcript	n.351-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
KIF19	ENST00000547389.1 linkuse as main transcript	n.325-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
KIF19	ENST00000551294.5 linkuse as main transcript	c.232-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000449134

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34972

AN:

151846

Hom.:

4715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0976

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.260

GnomAD3 exomes

AF:

0.285

AC:

71409

AN:

250558

Hom.:

10805

AF XY:

0.287

AC XY:

38913

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.0889

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.413

Gnomad EAS exome

AF:

0.346

Gnomad SAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.272

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.268

AC:

391148

AN:

1457642

Hom.:

54223

Cov.:

AF XY:

0.270

AC XY:

195999

AN XY:

725260

show subpopulations

Gnomad4 AFR exome

AF:

0.0900

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.410

Gnomad4 EAS exome

AF:

0.289

Gnomad4 SAS exome

AF:

0.305

Gnomad4 FIN exome

AF:

0.241

Gnomad4 NFE exome

AF:

0.264

Gnomad4 OTH exome

AF:

0.280

GnomAD4 genome

AF:

0.230

AC:

34975

AN:

151966

Hom.:

4715

Cov.:

AF XY:

0.234

AC XY:

17379

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0975

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.318

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.265

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.270

Hom.:

9366

Bravo

AF:

0.231

Asia WGS

AF:

0.286

AC:

992

AN:

3478

EpiCase

AF:

0.281

EpiControl

AF:

0.285

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Oct 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.0

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.050

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