dbSNP rs2817245: KIAA0319:c.3041-35C>T (chr6-24547378-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.3041-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,579,254 control chromosomes in the GnomAD database, including 28,854 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 0.23 ( 4698 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24156 hom. )

Consequence

KIAA0319
NM_014809.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.181

Publications

11 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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.3041-35C>T		intron_variant	Intron 20 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.3041-35C>T		intron_variant	Intron 20 of 20	1	NM_014809.4	ENSP00000367459.3		Q5VV43-1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34831

AN:

152016

Hom.:

4676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.372

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.232

GnomAD2 exomes

AF:

0.188

AC:

43143

AN:

229864

AF XY:

0.188

show subpopulations

Gnomad AFR exome

AF:

0.372

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.179

AC:

255581

AN:

1427118

Hom.:

24156

Cov.:

AF XY:

0.179

AC XY:

127241

AN XY:

709208

show subpopulations

African (AFR)

AF:

0.379

AC:

12411

AN:

32774

American (AMR)

AF:

0.141

AC:

6045

AN:

42832

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

4882

AN:

25778

East Asian (EAS)

AF:

0.0924

AC:

3602

AN:

38978

South Asian (SAS)

AF:

0.209

AC:

17729

AN:

84714

European-Finnish (FIN)

AF:

0.231

AC:

12098

AN:

52292

Middle Eastern (MID)

AF:

0.287

AC:

1629

AN:

5680

European-Non Finnish (NFE)

AF:

0.171

AC:

185957

AN:

1084898

Other (OTH)

AF:

0.190

AC:

11228

AN:

59172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

9851

19703

29554

39406

49257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6708

13416

20124

26832

33540

<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:

0.229

AC:

34887

AN:

152136

Hom.:

4698

Cov.:

AF XY:

0.231

AC XY:

17171

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.372

AC:

15430

AN:

41480

American (AMR)

AF:

0.174

AC:

2667

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

665

AN:

3470

East Asian (EAS)

AF:

0.106

AC:

547

AN:

5174

South Asian (SAS)

AF:

0.196

AC:

943

AN:

4808

European-Finnish (FIN)

AF:

0.235

AC:

2493

AN:

10592

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11524

AN:

68008

Other (OTH)

AF:

0.229

AC:

483

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1354

2707

4061

5414

6768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.185

Hom.:

2879

Bravo

AF:

0.231

Asia WGS

AF:

0.195

AC:

679

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.7

(source)

DANN

Benign

0.70

PhyloP100

0.18

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