rs807533

Positions:

• chr6-24549678-C-G
• chr6-24549678-C-T

Variant summary

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

The ENST00000378214.8(KIAA0319):​c.3040+1756G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,098 control chromosomes in the GnomAD database, including 27,984 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 0.58 (27984 hom., cov: 32)
• Consequence: KIAA0319 ENST00000378214.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

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 (NFE) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.3040+1756G>C		intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.3040+1756G>C		intron_variant		1	NM_014809.4	ENSP00000367459	P2

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88939 AN: 151980 Hom.: 27980 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.824

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.585 AC: 88965 AN: 152098 Hom.: 27984 Cov.: 32 AF XY: 0.582 AC XY: 43246 AN XY: 74324

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.577

Alfa AF: 0.654 Hom.: 4226

Bravo AF: 0.562

Asia WGS AF: 0.515 AC: 1793 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	1.0
DANN	Benign	0.72

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: rs807533; hg19: chr6-24549906;