rs807526

Positions:

• chr6-24543492-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047419602.1(KIAA0319):​c.3041-2147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,850 control chromosomes in the GnomAD database, including 5,541 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 0.26 (5541 hom., cov: 32)
• Consequence: KIAA0319 XM_047419602.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	XM_047419602.1	c.3041-2147C>T		intron_variant			XP_047275558.1
KIAA0319	XM_017011546.3	c.2858-2147C>T		intron_variant			XP_016867035.1
KIAA0319	XM_017011550.2	c.*13-2147C>T		intron_variant			XP_016867039.1
KIAA0319	XM_047419604.1	c.*13-2147C>T		intron_variant			XP_047275560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40071 AN: 151732 Hom.: 5521 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.264 AC: 40138 AN: 151850 Hom.: 5541 Cov.: 32 AF XY: 0.259 AC XY: 19187 AN XY: 74192

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.246

Alfa AF: 0.262 Hom.: 660

Bravo AF: 0.265

Asia WGS AF: 0.228 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs807526; hg19: chr6-24543720;