Variant 6-24554534-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_014809.4(KIAA0319):c.2948+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 0.238 in 1,602,474 control chromosomes in the GnomAD database, including 49,458 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 (no stars).

Frequency

Genomes: 𝑓 0.29 ( 7878 hom., cov: 32)

Exomes 𝑓: 0.23 ( 41580 hom. )

Consequence

KIAA0319
NM_014809.4 splice_region, intron

Scores

Splicing: ADA: 0.00009128

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.517

Variant links:

Genes affected

KIAA0319 (HGNC:21580): (KIAA0319) This gene encodes a transmembrane protein that contains a large extracellular domain with multiple polycystic kidney disease (PKD) domains. The encoded protein may play a role in the development of the cerebral cortex by regulating neuronal migration and cell adhesion. Single nucleotide polymorphisms in this gene are associated with dyslexia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

KIAA0319 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 6-24554534-T-C is Benign according to our data. Variant chr6-24554534-T-C is described in ClinVar as [Benign]. Clinvar id is 3060264.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4 linkuse as main transcript	c.2948+7A>G		splice_region_variant, intron_variant		ENST00000378214.8	NP_055624.2	Q5VV43-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8 linkuse as main transcript	c.2948+7A>G		splice_region_variant, intron_variant		1	NM_014809.4	ENSP00000367459.3		Q5VV43-1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44619

AN:

151992

Hom.:

7858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.279

GnomAD3 exomes

AF:

0.225

AC:

56430

AN:

251072

Hom.:

7309

AF XY:

0.223

AC XY:

30308

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.499

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.239

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.232

AC:

336492

AN:

1450364

Hom.:

41580

Cov.:

AF XY:

0.231

AC XY:

166962

AN XY:

722298

show subpopulations

Gnomad4 AFR exome

AF:

0.510

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.209

Gnomad4 EAS exome

AF:

0.106

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.237

GnomAD4 genome

AF:

0.294

AC:

44674

AN:

152110

Hom.:

7878

Cov.:

AF XY:

0.291

AC XY:

21647

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.496

Gnomad4 AMR

AF:

0.204

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.222

Gnomad4 OTH

AF:

0.276

Alfa

AF:

0.235

Hom.:

10340

Bravo

AF:

0.299

Asia WGS

AF:

0.214

AC:

743

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIAA0319-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.7

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000091

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.030

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