chr6-24613067-T-A

Variant names:

• chr6-24613067-T-A
• rs6939068
• NM_014809.4:c.-105-11859A>T

Variant summary

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

The NM_014809.4(KIAA0319):​c.-105-11859A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,202 control chromosomes in the GnomAD database, including 2,373 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 0.12 (2373 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 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.-105-11859A>T		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.-105-11859A>T		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.-105-11859A>T		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.-105-11859A>T		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.-105-11859A>T		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000535378.5	TSL:2	c.-223-11859A>T		intron	N/A	ENSP00000442403.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18898 AN: 152084 Hom.: 2364 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.124 AC: 18940 AN: 152202 Hom.: 2373 Cov.: 32 AF XY: 0.128 AC XY: 9533 AN XY: 74440

African (AFR) AF: 0.249 AC: 10342 AN: 41492

American (AMR) AF: 0.217 AC: 3322 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3472

East Asian (EAS) AF: 0.476 AC: 2465 AN: 5184

South Asian (SAS) AF: 0.119 AC: 575 AN: 4820

European-Finnish (FIN) AF: 0.0125 AC: 133 AN: 10620

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0248 AC: 1685 AN: 68012

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.0733 Hom.: 123

Bravo AF: 0.147

Asia WGS AF: 0.267 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.67
PhyloP100		0.012
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: rs6939068; hg19: chr6-24613295;