rs2235676

Positions:

• chr6-24645469-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.-106+267C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,190 control chromosomes in the GnomAD database, including 1,046 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 0.10 (1046 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319	NM_014809.4	c.-106+267C>A		intron_variant		ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8	c.-106+267C>A		intron_variant		1	NM_014809.4	P2
KIAA0319	ENST00000537886.5	c.-106+267C>A		intron_variant		1
KIAA0319	ENST00000430948.6	c.-81+158C>A		intron_variant		2		A2
KIAA0319	ENST00000535378.5	c.-224+267C>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15986 AN: 152072 Hom.: 1049 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.0900

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.105 AC: 15973 AN: 152190 Hom.: 1046 Cov.: 32 AF XY: 0.105 AC XY: 7811 AN XY: 74408

Gnomad4 AFR AF: 0.0431

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0862

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.0900

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.123

Alfa AF: 0.115 Hom.: 262

Bravo AF: 0.101

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.6
DANN	Benign	0.84

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: rs2235676; hg19: chr6-24645697;