6-24581804-C-G

Variant names:

• chr6-24581804-C-G
• rs807509
• NM_014809.4:c.1191+445G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014809.4(KIAA0319):​c.1191+445G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,068 control chromosomes in the GnomAD database, including 17,556 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 0.46 (17556 hom., cov: 31)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.1191+445G>C		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.1191+445G>C		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.1191+445G>C		intron	N/A	NP_001337332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.1191+445G>C		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.1191+445G>C		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.-538+445G>C		intron	N/A	ENSP00000483665.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69478 AN: 151948 Hom.: 17514 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.458 AC: 69585 AN: 152068 Hom.: 17556 Cov.: 31 AF XY: 0.452 AC XY: 33568 AN XY: 74332

African (AFR) AF: 0.686 AC: 28461 AN: 41480

American (AMR) AF: 0.355 AC: 5426 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1405 AN: 5162

South Asian (SAS) AF: 0.490 AC: 2362 AN: 4822

European-Finnish (FIN) AF: 0.314 AC: 3312 AN: 10548

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25918 AN: 67990

Other (OTH) AF: 0.456 AC: 962 AN: 2110

Alfa AF: 0.243 Hom.: 467

Bravo AF: 0.471

Asia WGS AF: 0.460 AC: 1600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.2
DANN	Benign	0.40
PhyloP100		-0.033
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs807509; hg19: chr6-24582032;