6-24632414-A-C

Variant names:

• chr6-24632414-A-C
• rs761100
• NM_014809.4:c.-106+13322T>G

Variant summary

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

The NM_014809.4(KIAA0319):​c.-106+13322T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,056 control chromosomes in the GnomAD database, including 29,034 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 0.61 (29034 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• Publications: 33 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 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.-106+13322T>G		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.-106+13213T>G		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.-106+13621T>G		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.-106+13322T>G		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.-106+13322T>G		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000535378.5	TSL:2	c.-224+13322T>G		intron	N/A	ENSP00000442403.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92955 AN: 151938 Hom.: 29021 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.612 AC: 93008 AN: 152056 Hom.: 29034 Cov.: 32 AF XY: 0.611 AC XY: 45410 AN XY: 74344

African (AFR) AF: 0.661 AC: 27427 AN: 41476

American (AMR) AF: 0.696 AC: 10634 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3470

East Asian (EAS) AF: 0.868 AC: 4492 AN: 5174

South Asian (SAS) AF: 0.644 AC: 3101 AN: 4812

European-Finnish (FIN) AF: 0.470 AC: 4957 AN: 10548

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38221 AN: 67984

Other (OTH) AF: 0.620 AC: 1311 AN: 2114

Alfa AF: 0.580 Hom.: 50293

Bravo AF: 0.632

Asia WGS AF: 0.745 AC: 2591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		0.36
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: rs761100; hg19: chr6-24632642;