6-24563324-C-T

Position:

• chr6-24563324-C-T

Variant summary

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

The NM_014809.4(KIAA0319):​c.2591+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,578,904 control chromosomes in the GnomAD database, including 1,221 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 0.050 (435 hom., cov: 33)
  • Exomes 𝑓: 0.024 (786 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2591+35G>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.2591+35G>A		intron_variant		1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7619 AN: 152164 Hom.: 433 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0421

GnomAD3 exomes AF: 0.0217 AC: 5029 AN: 231992 Hom.: 195 AF XY: 0.0187 AC XY: 2344 AN XY: 125062

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0130

Gnomad ASJ exome AF: 0.00184

Gnomad EAS exome AF: 0.000903

Gnomad SAS exome AF: 0.00182

Gnomad FIN exome AF: 0.00339

Gnomad NFE exome AF: 0.0200

Gnomad OTH exome AF: 0.0165

GnomAD4 exome AF: 0.0239 AC: 34063 AN: 1426622 Hom.: 786 Cov.: 30 AF XY: 0.0228 AC XY: 16082 AN XY: 705114

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0135

Gnomad4 ASJ exome AF: 0.00186

Gnomad4 EAS exome AF: 0.000488

Gnomad4 SAS exome AF: 0.00213

Gnomad4 FIN exome AF: 0.00346

Gnomad4 NFE exome AF: 0.0244

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.0501 AC: 7627 AN: 152282 Hom.: 435 Cov.: 33 AF XY: 0.0470 AC XY: 3500 AN XY: 74472

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0225

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.0207

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0176 Hom.: 19

Bravo AF: 0.0563

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.68

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: rs2744549; hg19: chr6-24563552;