6-24542035-G-A

Position:

• chr6-24542035-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.3041-690C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,116 control chromosomes in the GnomAD database, including 13,716 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 0.41 (13716 hom., cov: 33)
• Consequence: KIAA0319 XM_047419602.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	XM_047419602.1	c.3041-690C>T		intron_variant			XP_047275558.1
KIAA0319	XM_017011546.3	c.2858-690C>T		intron_variant			XP_016867035.1
KIAA0319	XM_017011550.2	c.*13-690C>T		intron_variant			XP_016867039.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61802 AN: 151996 Hom.: 13723 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.406 AC: 61788 AN: 152116 Hom.: 13716 Cov.: 33 AF XY: 0.407 AC XY: 30282 AN XY: 74358

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.404

Alfa AF: 0.456 Hom.: 2080

Bravo AF: 0.385

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2817241; hg19: chr6-24542263;