rs2745333

Positions:

• chr6-24617969-A-G

Variant summary

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

The ENST00000378214.8(KIAA0319):​c.-105-16761T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,894 control chromosomes in the GnomAD database, including 39,601 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 0.71 (39601 hom., cov: 30)
• Consequence: KIAA0319 ENST00000378214.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.-105-16761T>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.-105-16761T>C		intron_variant		1	NM_014809.4	ENSP00000367459	P2
KIAA0319	ENST00000537886.5	c.-105-16761T>C		intron_variant		1		ENSP00000439700
KIAA0319	ENST00000430948.6	c.-80-21351T>C		intron_variant		2		ENSP00000401086	A2
KIAA0319	ENST00000535378.5	c.-223-16761T>C		intron_variant		2		ENSP00000442403	A2

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107004 AN: 151776 Hom.: 39546 Cov.: 30

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.705 AC: 107115 AN: 151894 Hom.: 39601 Cov.: 30 AF XY: 0.701 AC XY: 52020 AN XY: 74238

Gnomad4 AFR AF: 0.915

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.728

Alfa AF: 0.643 Hom.: 4019

Bravo AF: 0.737

Asia WGS AF: 0.811 AC: 2821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.28

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: rs2745333; hg19: chr6-24618197;