6-24631330-T-C

Variant names:

• chr6-24631330-T-C
• rs6456622
• NM_014809.4:c.-106+14406A>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+14406A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,114 control chromosomes in the GnomAD database, including 38,383 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 (38383 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.22
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.-106+14406A>G		intron	N/A	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.-106+14297A>G		intron	N/A	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.-106+14705A>G		intron	N/A	NP_001337332.1	Q5VV43-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.-106+14406A>G		intron	N/A	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.-106+14406A>G		intron	N/A	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000901508.1		c.-106+14705A>G		intron	N/A	ENSP00000571567.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107161 AN: 151996 Hom.: 38356 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.705 AC: 107239 AN: 152114 Hom.: 38383 Cov.: 32 AF XY: 0.702 AC XY: 52173 AN XY: 74364

African (AFR) AF: 0.798 AC: 33120 AN: 41496

American (AMR) AF: 0.772 AC: 11801 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2208 AN: 3472

East Asian (EAS) AF: 0.873 AC: 4518 AN: 5174

South Asian (SAS) AF: 0.694 AC: 3347 AN: 4822

European-Finnish (FIN) AF: 0.539 AC: 5688 AN: 10554

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.648 AC: 44087 AN: 67988

Other (OTH) AF: 0.717 AC: 1517 AN: 2116

Alfa AF: 0.644 Hom.: 3753

Bravo AF: 0.727

Asia WGS AF: 0.792 AC: 2752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.34
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6456622; hg19: chr6-24631558;