dbSNP rs2744564: KIAA0319:c.1280-35G>C (chr6-24579985-C-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.1280-35G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,462,394 control chromosomes in the GnomAD database, including 2,171 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 0.072 ( 935 hom., cov: 31)

Exomes 𝑓: 0.028 ( 1236 hom. )

Consequence

KIAA0319
NM_014809.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

1 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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.1280-35G>C		intron_variant	Intron 7 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.1280-35G>C		intron_variant	Intron 7 of 20	1	NM_014809.4	ENSP00000367459.3		Q5VV43-1

Frequencies

GnomAD3 genomes

AF:

0.0714

AC:

10860

AN:

152024

Hom.:

930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0323

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00321

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0219

Gnomad OTH

AF:

0.0589

GnomAD2 exomes

AF:

0.0264

AC:

4449

AN:

168250

AF XY:

0.0218

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.00612

Gnomad EAS exome

AF:

0.000965

Gnomad FIN exome

AF:

0.00349

Gnomad NFE exome

AF:

0.0231

Gnomad OTH exome

AF:

0.0203

GnomAD4 exome

AF:

0.0276

AC:

36176

AN:

1310252

Hom.:

1236

Cov.:

AF XY:

0.0261

AC XY:

17015

AN XY:

652432

show subpopulations

African (AFR)

AF:

0.226

AC:

6823

AN:

30254

American (AMR)

AF:

0.0201

AC:

741

AN:

36922

Ashkenazi Jewish (ASJ)

AF:

0.00683

AC:

168

AN:

24584

East Asian (EAS)

AF:

0.000467

AC:

AN:

36418

South Asian (SAS)

AF:

0.00241

AC:

187

AN:

77716

European-Finnish (FIN)

AF:

0.00332

AC:

166

AN:

50060

Middle Eastern (MID)

AF:

0.0257

AC:

142

AN:

5522

European-Non Finnish (NFE)

AF:

0.0263

AC:

26088

AN:

993690

Other (OTH)

AF:

0.0335

AC:

1844

AN:

55086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1598

3196

4794

6392

7990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1132

2264

3396

4528

5660

<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:

0.0716

AC:

10897

AN:

152142

Hom.:

935

Cov.:

AF XY:

0.0684

AC XY:

5091

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.210

AC:

8703

AN:

41462

American (AMR)

AF:

0.0323

AC:

494

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.00186

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00321

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0219

AC:

1487

AN:

67988

Other (OTH)

AF:

0.0583

AC:

123

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

453

906

1360

1813

2266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0410

Hom.:

Bravo

AF:

0.0811

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.029

(source)

DANN

Benign

0.32

PhyloP100

-1.3

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