dbSNP rs2038135: KIAA0319:c.-109A>C (chr6-24645739-T-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.-109A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,554 control chromosomes in the GnomAD database, including 37,902 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 0.70 ( 37812 hom., cov: 29)

Exomes 𝑓: 0.64 ( 90 hom. )

Consequence

KIAA0319
NM_014809.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.813

Publications

12 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=-0.85).

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.-109A>C		5_prime_UTR_variant	Exon 1 of 21	ENST00000378214.8	NP_055624.2	Q5VV43-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIAA0319	ENST00000378214.8 link	c.-109A>C	5_prime_UTR_variant	Exon 1 of 21	1	NM_014809.4	ENSP00000367459.3	Q5VV43-1
KIAA0319	ENST00000537886.5 link	c.-109A>C	5_prime_UTR_variant	Exon 1 of 19	1		ENSP00000439700.1	Q5VV43-4
KIAA0319	ENST00000535378.5 link	c.-227A>C	5_prime_UTR_variant	Exon 1 of 22	2		ENSP00000442403.1	Q5VV43-2
KIAA0319	ENST00000430948.6 link	c.-193A>C	5_prime_UTR_variant	Exon 1 of 20	2		ENSP00000401086.2	Q5VV43-3

Frequencies

GnomAD3 genomes

AF:

0.702

AC:

106048

AN:

151022

Hom.:

37783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.796

Gnomad AMI

AF:

0.784

Gnomad AMR

AF:

0.767

Gnomad ASJ

AF:

0.621

Gnomad EAS

AF:

0.872

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.799

Gnomad NFE

AF:

0.646

Gnomad OTH

AF:

0.705

GnomAD4 exome

AF:

0.641

AC:

264

AN:

412

Hom.:

Cov.:

AF XY:

0.645

AC XY:

160

AN XY:

248

show subpopulations

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.786

AC:

AN:

East Asian (EAS)

AF:

0.833

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.684

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.609

AC:

184

AN:

302

Other (OTH)

AF:

0.850

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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:

0.702

AC:

106129

AN:

151142

Hom.:

37812

Cov.:

AF XY:

0.699

AC XY:

51571

AN XY:

73812

show subpopulations

African (AFR)

AF:

0.795

AC:

32794

AN:

41228

American (AMR)

AF:

0.767

AC:

11646

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.621

AC:

2144

AN:

3452

East Asian (EAS)

AF:

0.872

AC:

4445

AN:

5096

South Asian (SAS)

AF:

0.695

AC:

3322

AN:

4778

European-Finnish (FIN)

AF:

0.537

AC:

5636

AN:

10488

Middle Eastern (MID)

AF:

0.802

AC:

231

AN:

288

European-Non Finnish (NFE)

AF:

0.646

AC:

43720

AN:

67638

Other (OTH)

AF:

0.710

AC:

1490

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

1577

3154

4731

6308

7885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<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:

0.670

Hom.:

36809

Bravo

AF:

0.724

Asia WGS

AF:

0.790

AC:

2745

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.9

(source)

DANN

Benign

0.81

PhyloP100

-0.81

PromoterAI

-0.030

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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