NM_014809.4:c.-105-5875G>A

Variant names:

• chr6-24607083-C-T
• rs6911855
• NM_014809.4:c.-105-5875G>A

Variant summary

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

The NM_014809.4(KIAA0319):​c.-105-5875G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,262 control chromosomes in the GnomAD database, including 2,315 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 (2315 hom., cov: 33)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 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.-105-5875G>A		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.-105-5875G>A		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.-105-5875G>A		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.-105-5875G>A		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.-105-5875G>A		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000535378.5	TSL:2	c.-223-5875G>A		intron	N/A	ENSP00000442403.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18377 AN: 152144 Hom.: 2306 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0113

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0195

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.121 AC: 18423 AN: 152262 Hom.: 2315 Cov.: 33 AF XY: 0.124 AC XY: 9258 AN XY: 74456

African (AFR) AF: 0.250 AC: 10386 AN: 41528

American (AMR) AF: 0.213 AC: 3260 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2355 AN: 5184

South Asian (SAS) AF: 0.117 AC: 567 AN: 4828

European-Finnish (FIN) AF: 0.0113 AC: 120 AN: 10620

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0195 AC: 1328 AN: 68030

Other (OTH) AF: 0.125 AC: 264 AN: 2112

Alfa AF: 0.0762 Hom.: 147

Bravo AF: 0.142

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.4
DANN	Benign	0.32
PhyloP100		-0.66
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: rs6911855; hg19: chr6-24607311;