dbSNP rs2760157: KIAA0319:c.1505+66C>T (chr6-24578044-G-A) – 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.1505+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,492,276 control chromosomes in the GnomAD database, including 40,997 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 0.28 ( 7089 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33908 hom. )

Consequence

KIAA0319
NM_014809.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.495

Publications

12 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:

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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=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.1505+66C>T		intron_variant	Intron 9 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.1505+66C>T		intron_variant	Intron 9 of 20	1	NM_014809.4	ENSP00000367459.3		Q5VV43-1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42766

AN:

151776

Hom.:

7071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.210

AC:

280928

AN:

1340382

Hom.:

33908

AF XY:

0.207

AC XY:

136884

AN XY:

662550

show subpopulations

African (AFR)

AF:

0.439

AC:

13013

AN:

29614

American (AMR)

AF:

0.422

AC:

12757

AN:

30234

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

3684

AN:

22040

East Asian (EAS)

AF:

0.534

AC:

20294

AN:

37984

South Asian (SAS)

AF:

0.170

AC:

11740

AN:

68960

European-Finnish (FIN)

AF:

0.251

AC:

12624

AN:

50250

Middle Eastern (MID)

AF:

0.169

AC:

899

AN:

5326

European-Non Finnish (NFE)

AF:

0.186

AC:

193456

AN:

1040564

Other (OTH)

AF:

0.225

AC:

12461

AN:

55410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

10081

20163

30244

40326

50407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7390

14780

22170

29560

36950

<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:

0.282

AC:

42840

AN:

151894

Hom.:

7089

Cov.:

AF XY:

0.286

AC XY:

21202

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.424

AC:

17530

AN:

41388

American (AMR)

AF:

0.356

AC:

5431

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

592

AN:

3468

East Asian (EAS)

AF:

0.529

AC:

2721

AN:

5146

South Asian (SAS)

AF:

0.192

AC:

924

AN:

4818

European-Finnish (FIN)

AF:

0.259

AC:

2723

AN:

10530

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12230

AN:

67980

Other (OTH)

AF:

0.255

AC:

537

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1483

2965

4448

5930

7413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.207

Hom.:

5463

Bravo

AF:

0.297

Asia WGS

AF:

0.324

AC:

1125

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.97

(source)

DANN

Benign

0.54

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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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