NM_014809.4:c.1734+559T>C

Variant names:

• chr6-24575809-A-G
• rs807525
• NM_014809.4:c.1734+559T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014809.4(KIAA0319):​c.1734+559T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0948 in 152,190 control chromosomes in the GnomAD database, including 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 0.095 (696 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 6 publications found

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]

ACMG classification

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 = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.1734+559T>C		intron_variant	Intron 10 of 20	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.1734+559T>C		intron_variant	Intron 10 of 20	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14405 AN: 152072 Hom.: 695 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0815

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.0938

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0948 AC: 14431 AN: 152190 Hom.: 696 Cov.: 32 AF XY: 0.0929 AC XY: 6912 AN XY: 74404

African (AFR) AF: 0.114 AC: 4722 AN: 41510

American (AMR) AF: 0.0818 AC: 1251 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 293 AN: 3468

East Asian (EAS) AF: 0.0764 AC: 397 AN: 5194

South Asian (SAS) AF: 0.107 AC: 515 AN: 4820

European-Finnish (FIN) AF: 0.0712 AC: 754 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0910 AC: 6187 AN: 67998

Other (OTH) AF: 0.0947 AC: 200 AN: 2112

Alfa AF: 0.0926 Hom.: 371

Bravo AF: 0.0978

Asia WGS AF: 0.0920 AC: 321 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.88
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs807525; hg19: chr6-24576037;