chr6-24560105-C-T

Position:

• chr6-24560105-C-T

Variant summary

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

The ENST00000378214.8(KIAA0319):​c.2592-950G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,064 control chromosomes in the GnomAD database, including 57,688 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 0.86 (57688 hom., cov: 34)
• Consequence: KIAA0319 ENST00000378214.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2592-950G>A		intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2592-950G>A		intron_variant		1	NM_014809.4	ENSP00000367459	P2

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131356 AN: 151946 Hom.: 57654 Cov.: 34

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.864 AC: 131439 AN: 152064 Hom.: 57688 Cov.: 34 AF XY: 0.858 AC XY: 63787 AN XY: 74312

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.922

Gnomad4 OTH AF: 0.854

Alfa AF: 0.899 Hom.: 7689

Bravo AF: 0.849

Asia WGS AF: 0.705 AC: 2454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.047
DANN	Benign	0.26

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: rs807542; hg19: chr6-24560333;