Genetic Variant KIAA0319:c.-106+17C>G (chr6-24645719-G-C) – 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.-106+17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,418 control chromosomes in the GnomAD database, including 36,681 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 0.69 ( 36608 hom., cov: 29)

Exomes 𝑓: 0.62 ( 73 hom. )

Consequence

KIAA0319
NM_014809.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.680

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:

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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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.-106+17C>G		intron_variant	Intron 1 of 20	ENST00000378214.8	NP_055624.2	Q5VV43-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIAA0319	ENST00000378214.8 link	c.-106+17C>G	intron_variant	Intron 1 of 20	1	NM_014809.4	ENSP00000367459.3	Q5VV43-1
KIAA0319	ENST00000537886.5 link	c.-106+17C>G	intron_variant	Intron 1 of 18	1		ENSP00000439700.1	Q5VV43-4
KIAA0319	ENST00000430948.6 link	c.-173C>G	5_prime_UTR_variant	Exon 1 of 20	2		ENSP00000401086.2	Q5VV43-3
KIAA0319	ENST00000535378.5 link	c.-224+17C>G	intron_variant	Intron 1 of 21	2		ENSP00000442403.1	Q5VV43-2

Frequencies

GnomAD3 genomes

AF:

0.690

AC:

104120

AN:

150930

Hom.:

36581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.793

Gnomad AMI

AF:

0.784

Gnomad AMR

AF:

0.760

Gnomad ASJ

AF:

0.620

Gnomad EAS

AF:

0.873

Gnomad SAS

AF:

0.694

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.799

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.700

GnomAD4 exome

AF:

0.617

AC:

227

AN:

368

Hom.:

Cov.:

AF XY:

0.600

AC XY:

132

AN XY:

220

show subpopulations

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.900

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.679

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.593

AC:

166

AN:

280

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.690

AC:

104199

AN:

151050

Hom.:

36608

Cov.:

AF XY:

0.686

AC XY:

50572

AN XY:

73742

show subpopulations

African (AFR)

AF:

0.793

AC:

32643

AN:

41180

American (AMR)

AF:

0.760

AC:

11534

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

2141

AN:

3456

East Asian (EAS)

AF:

0.873

AC:

4447

AN:

5096

South Asian (SAS)

AF:

0.692

AC:

3306

AN:

4778

European-Finnish (FIN)

AF:

0.500

AC:

5228

AN:

10456

Middle Eastern (MID)

AF:

0.802

AC:

231

AN:

288

European-Non Finnish (NFE)

AF:

0.628

AC:

42500

AN:

67642

Other (OTH)

AF:

0.704

AC:

1468

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1601

3203

4804

6406

8007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.509

Hom.:

1255

Bravo

AF:

0.715

Asia WGS

AF:

0.790

AC:

2746

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.7

(source)

DANN

Benign

0.67

PhyloP100

0.68

PromoterAI

-0.022

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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