dbSNP rs2076313: KIAA0319:c.3040+38T>C (chr6-24551396-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.3040+38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,425,996 control chromosomes in the GnomAD database, including 46,904 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 0.30 ( 7971 hom., cov: 31)

Exomes 𝑓: 0.24 ( 38933 hom. )

Consequence

KIAA0319
NM_014809.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.75

Publications

5 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.3040+38T>C		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.3040+38T>C		intron_variant	Intron 20 of 20	1	NM_014809.4	ENSP00000367459.3		Q5VV43-1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

45033

AN:

151894

Hom.:

7951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.284

GnomAD2 exomes

AF:

0.229

AC:

57277

AN:

250150

AF XY:

0.228

show subpopulations

Gnomad AFR exome

AF:

0.499

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.240

AC:

305305

AN:

1273984

Hom.:

38933

Cov.:

AF XY:

0.238

AC XY:

153445

AN XY:

643724

show subpopulations

African (AFR)

AF:

0.515

AC:

15334

AN:

29782

American (AMR)

AF:

0.162

AC:

7215

AN:

44416

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

5418

AN:

25158

East Asian (EAS)

AF:

0.106

AC:

4108

AN:

38860

South Asian (SAS)

AF:

0.241

AC:

19910

AN:

82596

European-Finnish (FIN)

AF:

0.259

AC:

13800

AN:

53316

Middle Eastern (MID)

AF:

0.324

AC:

1762

AN:

5446

European-Non Finnish (NFE)

AF:

0.239

AC:

224534

AN:

940130

Other (OTH)

AF:

0.244

AC:

13224

AN:

54280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

11276

22552

33829

45105

56381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7316

14632

21948

29264

36580

<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:

0.297

AC:

45088

AN:

152012

Hom.:

7971

Cov.:

AF XY:

0.294

AC XY:

21844

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.497

AC:

20579

AN:

41424

American (AMR)

AF:

0.207

AC:

3157

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

743

AN:

3468

East Asian (EAS)

AF:

0.109

AC:

567

AN:

5180

South Asian (SAS)

AF:

0.223

AC:

1074

AN:

4822

European-Finnish (FIN)

AF:

0.260

AC:

2749

AN:

10568

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15425

AN:

67960

Other (OTH)

AF:

0.281

AC:

593

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1513

3027

4540

6054

7567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.265

Hom.:

1375

Bravo

AF:

0.302

Asia WGS

AF:

0.215

AC:

747

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.18

(source)

DANN

Benign

0.36

PhyloP100

-2.8

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