rs807544

Positions:

• chr6-24562074-T-G

Variant summary

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

The NM_014809.4(KIAA0319):​c.2591+1285A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 152,220 control chromosomes in the GnomAD database, including 756 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 0.096 (756 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319	NM_014809.4	c.2591+1285A>C		intron_variant		ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2591+1285A>C		intron_variant		1	NM_014809.4	P2

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14547 AN: 152102 Hom.: 755 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0857

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.0941

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

GnomAD4 genome AF: 0.0957 AC: 14573 AN: 152220 Hom.: 756 Cov.: 32 AF XY: 0.0934 AC XY: 6950 AN XY: 74424

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0792

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.0859

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0674

Gnomad4 NFE AF: 0.0843

Gnomad4 OTH AF: 0.0950

Alfa AF: 0.0902 Hom.: 73

Bravo AF: 0.0999

Asia WGS AF: 0.0920 AC: 321 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	0.46
DANN	Benign	0.62

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: rs807544; hg19: chr6-24562302;