dbSNP rs2038137: KIAA0319:c.-106+21A>C (chr6-24645715-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_001168375.2(KIAA0319):c.-194A>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 0.69 in 151,480 control chromosomes in the GnomAD database, including 36,696 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 ( 36623 hom., cov: 29)

Exomes 𝑓: 0.62 ( 73 hom. )

Consequence

KIAA0319
NM_001168375.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0560

Publications

33 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168375.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIAA0319	NM_014809.4	MANE Select	c.-106+21A>C	intron	N/A	NP_055624.2	Q5VV43-1
KIAA0319	NM_001168375.2		c.-194A>C	5_prime_UTR	Exon 1 of 21	NP_001161847.1	Q5VV43-1
KIAA0319	NM_001350405.2		c.-194A>C	5_prime_UTR	Exon 1 of 20	NP_001337334.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.-106+21A>C	intron	N/A	ENSP00000367459.3	Q5VV43-1
KIAA0319	ENST00000537886.5	TSL:1	c.-106+21A>C	intron	N/A	ENSP00000439700.1	Q5VV43-4
KIAA0319	ENST00000937457.1		c.-194A>C	5_prime_UTR	Exon 1 of 21	ENSP00000607516.1

Frequencies

GnomAD3 genomes

AF:

0.690

AC:

104159

AN:

150996

Hom.:

36596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.793

Gnomad AMI

AF:

0.785

Gnomad AMR

AF:

0.760

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.873

Gnomad SAS

AF:

0.694

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.799

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.699

GnomAD4 exome

AF:

0.618

AC:

225

AN:

364

Hom.:

Cov.:

AF XY:

0.613

AC XY:

125

AN XY:

204

show subpopulations

African (AFR)

AF:

0.375

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:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.588

AC:

160

AN:

272

Other (OTH)

AF:

0.700

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

104238

AN:

151116

Hom.:

36623

Cov.:

AF XY:

0.686

AC XY:

50601

AN XY:

73780

show subpopulations

African (AFR)

AF:

0.793

AC:

32661

AN:

41206

American (AMR)

AF:

0.760

AC:

11545

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2139

AN:

3454

East Asian (EAS)

AF:

0.873

AC:

4447

AN:

5094

South Asian (SAS)

AF:

0.692

AC:

3312

AN:

4786

European-Finnish (FIN)

AF:

0.501

AC:

5239

AN:

10466

Middle Eastern (MID)

AF:

0.802

AC:

231

AN:

288

European-Non Finnish (NFE)

AF:

0.628

AC:

42489

AN:

67636

Other (OTH)

AF:

0.704

AC:

1472

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1619

3237

4856

6474

8093

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:

0.652

Hom.:

4122

Bravo

AF:

0.715

Asia WGS

AF:

0.790

AC:

2746

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.8

(source)

DANN

Benign

0.57

PhyloP100

-0.056

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=299/1

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