rs699463

Positions:

• chr6-24544675-G-A

Variant summary

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

The NM_014809.4(KIAA0319):​c.*2490C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,044 control chromosomes in the GnomAD database, including 5,518 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 0.26 (5517 hom., cov: 32)
  • Exomes 𝑓: 0.19 (1 hom.)
• Consequence: KIAA0319 NM_014809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.*2490C>T		3_prime_UTR_variant	21/21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.*2490C>T		3_prime_UTR_variant	21/21	1	NM_014809.4	ENSP00000367459	P2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39970 AN: 151908 Hom.: 5496 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 1 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.214

GnomAD4 genome AF: 0.263 AC: 40038 AN: 152028 Hom.: 5517 Cov.: 32 AF XY: 0.258 AC XY: 19161 AN XY: 74328

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.244

Alfa AF: 0.250 Hom.: 8341

Bravo AF: 0.263

Asia WGS AF: 0.230 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.32
DANN	Benign	0.70

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: rs699463; hg19: chr6-24544903;