rs807508

Positions:

• chr6-24581055-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.1192-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,256,466 control chromosomes in the GnomAD database, including 5,582 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 0.094 (687 hom., cov: 32)
  • Exomes 𝑓: 0.092 (4895 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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 = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.1192-42C>T		intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.1192-42C>T		intron_variant		1	NM_014809.4	ENSP00000367459	P2

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14312 AN: 152088 Hom.: 686 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0851

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0901

Gnomad OTH AF: 0.0942

GnomAD3 exomes AF: 0.0911 AC: 22213 AN: 243846 Hom.: 1070 AF XY: 0.0905 AC XY: 11994 AN XY: 132550

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.0898

Gnomad ASJ exome AF: 0.0775

Gnomad EAS exome AF: 0.0842

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.0732

Gnomad NFE exome AF: 0.0896

Gnomad OTH exome AF: 0.0944

GnomAD4 exome AF: 0.0917 AC: 101242 AN: 1104260 Hom.: 4895 Cov.: 15 AF XY: 0.0919 AC XY: 52006 AN XY: 566192

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0897

Gnomad4 ASJ exome AF: 0.0780

Gnomad4 EAS exome AF: 0.0573

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0745

Gnomad4 NFE exome AF: 0.0923

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0942 AC: 14339 AN: 152206 Hom.: 687 Cov.: 32 AF XY: 0.0923 AC XY: 6872 AN XY: 74416

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0817

Gnomad4 ASJ AF: 0.0851

Gnomad4 EAS AF: 0.0748

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0715

Gnomad4 NFE AF: 0.0901

Gnomad4 OTH AF: 0.0951

Alfa AF: 0.0895 Hom.: 657

Bravo AF: 0.0970

Asia WGS AF: 0.0920 AC: 319 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	0.070
DANN	Benign	0.67

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: rs807508; hg19: chr6-24581283;