6-24550765-C-G

Position:

• chr6-24550765-C-G

Variant summary

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

The NM_014809.4(KIAA0319):​c.3040+669G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 151,728 control chromosomes in the GnomAD database, including 10,733 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 0.35 (10733 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.3040+669G>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.3040+669G>C		intron_variant		1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53670 AN: 151608 Hom.: 10702 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.354 AC: 53745 AN: 151728 Hom.: 10733 Cov.: 32 AF XY: 0.351 AC XY: 25990 AN XY: 74130

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.327

Alfa AF: 0.165 Hom.: 294

Bravo AF: 0.355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.031
DANN	Benign	0.33

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: rs2760179; hg19: chr6-24550993;