6-24644967-G-C

Position:

• chr6-24644967-G-C

Variant summary

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

The NM_014809.4(KIAA0319):​c.-106+769C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,040 control chromosomes in the GnomAD database, including 38,136 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 0.70 (38136 hom., cov: 33)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.-106+769C>G		intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.-106+769C>G		intron_variant		1	NM_014809.4	ENSP00000367459	P2
KIAA0319	ENST00000537886.5	c.-106+769C>G		intron_variant		1		ENSP00000439700
KIAA0319	ENST00000430948.6	c.-81+660C>G		intron_variant		2		ENSP00000401086	A2
KIAA0319	ENST00000535378.5	c.-224+769C>G		intron_variant		2		ENSP00000442403	A2

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106814 AN: 151922 Hom.: 38108 Cov.: 33

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.703 AC: 106893 AN: 152040 Hom.: 38136 Cov.: 33 AF XY: 0.700 AC XY: 51974 AN XY: 74292

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.712

Alfa AF: 0.664 Hom.: 3962

Bravo AF: 0.724

Asia WGS AF: 0.792 AC: 2746 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.2
DANN	Benign	0.64

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: rs2328846; hg19: chr6-24645195;