6-24575809-A-G

Position:

• chr6-24575809-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
KIAA0319	NM_014809.4	c.1734+559T>C		intron_variant		ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8	c.1734+559T>C		intron_variant		1	NM_014809.4	P2

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

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0818

Gnomad4 ASJ AF: 0.0845

Gnomad4 EAS AF: 0.0764

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0712

Gnomad4 NFE AF: 0.0910

Gnomad4 OTH AF: 0.0947

Alfa AF: 0.0922 Hom.: 328

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

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

LitVar

Other links and lift over

dbSNP: rs807525; hg19: chr6-24576037;