rs807536

chr6-24554046-G-T

Variant summary

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

The NM_014809.4(KIAA0319):c.2948+495C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,208 control chromosomes in the GnomAD database, including 2,950 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 0.19 (2950 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319	NM_014809.4	c.2948+495C>A		intron_variant		ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2948+495C>A		intron_variant		1	NM_014809.4	P2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29017 AN: 152088 Hom.: 2943 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.191 AC: 29045 AN: 152208 Hom.: 2950 Cov.: 32 AF XY: 0.188 AC XY: 14002 AN XY: 74416

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.188

Alfa AF: 0.200 Hom.: 520

Bravo AF: 0.186

Asia WGS AF: 0.201 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.7
Dann	Benign	0.46

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: rs807536; hg19: chr6-24554274;