dbSNP rs2760163: KIAA0319:c.2293-11T>C (chr6-24564351-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014809.4(KIAA0319):c.2293-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 1,612,004 control chromosomes in the GnomAD database, including 1,213 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.050 ( 421 hom., cov: 32)

Exomes 𝑓: 0.023 ( 792 hom. )

Consequence

KIAA0319
NM_014809.4 intron

Scores

Splicing: ADA: 0.05520

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.2293-11T>C		intron_variant	Intron 14 of 20	ENST00000378214.8	NP_055624.2	Q5VV43-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8 link	c.2293-11T>C		intron_variant	Intron 14 of 20	1	NM_014809.4	ENSP00000367459.3		Q5VV43-1

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7570

AN:

152152

Hom.:

419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0225

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0420

GnomAD2 exomes

AF:

0.0208

AC:

5190

AN:

249516

AF XY:

0.0180

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.000871

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0151

GnomAD4 exome

AF:

0.0230

AC:

33585

AN:

1459734

Hom.:

792

Cov.:

AF XY:

0.0219

AC XY:

15922

AN XY:

726272

show subpopulations

African (AFR)

AF:

0.145

AC:

4827

AN:

33292

American (AMR)

AF:

0.0132

AC:

590

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00180

AC:

AN:

26132

East Asian (EAS)

AF:

0.000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00187

AC:

161

AN:

86246

European-Finnish (FIN)

AF:

0.00343

AC:

183

AN:

53404

Middle Eastern (MID)

AF:

0.0196

AC:

113

AN:

5762

European-Non Finnish (NFE)

AF:

0.0235

AC:

26110

AN:

1110146

Other (OTH)

AF:

0.0254

AC:

1534

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.407

Heterozygous variant carriers

1341

2681

4022

5362

6703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1100

2200

3300

4400

5500

<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:

0.0498

AC:

7577

AN:

152270

Hom.:

421

Cov.:

AF XY:

0.0468

AC XY:

3482

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.137

AC:

5671

AN:

41510

American (AMR)

AF:

0.0224

AC:

343

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5188

South Asian (SAS)

AF:

0.00228

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00320

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0207

AC:

1409

AN:

68032

Other (OTH)

AF:

0.0416

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

341

682

1022

1363

1704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0396

Hom.:

Bravo

AF:

0.0561

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.58

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.055

dbscSNV1_RF

Benign

0.19

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over