Genetic Variant NM_014809.4:c.1859-81T>C (chr6-24570116-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.1859-81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,371,906 control chromosomes in the GnomAD database, including 1,099 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 ( 434 hom., cov: 32)

Exomes 𝑓: 0.023 ( 665 hom. )

Consequence

KIAA0319
NM_014809.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

2 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=-0.83).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KIAA0319	NM_014809.4	MANE Select	c.1859-81T>C	intron	N/A	NP_055624.2
KIAA0319	NM_001168375.2		c.1859-81T>C	intron	N/A	NP_001161847.1
KIAA0319	NM_001350403.2		c.1859-81T>C	intron	N/A	NP_001337332.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.1859-81T>C	intron	N/A	ENSP00000367459.3
KIAA0319	ENST00000537886.5	TSL:1	c.1859-81T>C	intron	N/A	ENSP00000439700.1
KIAA0319	ENST00000616673.4	TSL:1	c.92-81T>C	intron	N/A	ENSP00000483665.1

Frequencies

GnomAD3 genomes

AF:

0.0500

AC:

7613

AN:

152144

Hom.:

433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0221

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0209

Gnomad OTH

AF:

0.0412

GnomAD4 exome

AF:

0.0235

AC:

28660

AN:

1219644

Hom.:

665

AF XY:

0.0223

AC XY:

13533

AN XY:

607772

show subpopulations

African (AFR)

AF:

0.147

AC:

4192

AN:

28532

American (AMR)

AF:

0.0139

AC:

502

AN:

36160

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

22024

East Asian (EAS)

AF:

0.000487

AC:

AN:

36932

South Asian (SAS)

AF:

0.00196

AC:

142

AN:

72332

European-Finnish (FIN)

AF:

0.00330

AC:

156

AN:

47252

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

3704

European-Non Finnish (NFE)

AF:

0.0241

AC:

22187

AN:

921066

Other (OTH)

AF:

0.0261

AC:

1349

AN:

51642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1339

2679

4018

5358

6697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.0500

AC:

7617

AN:

152262

Hom.:

434

Cov.:

AF XY:

0.0469

AC XY:

3495

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.137

AC:

5708

AN:

41536

American (AMR)

AF:

0.0221

AC:

338

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3468

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.00228

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00320

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0209

AC:

1420

AN:

68018

Other (OTH)

AF:

0.0408

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

355

709

1064

1418

1773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0369

Hom.:

Bravo

AF:

0.0561

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.7

(source)

DANN

Benign

0.84

PhyloP100

2.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over