6-24627975-T-C

Variant names:

• chr6-24627975-T-C
• rs2179515
• NM_014809.4:c.-106+17761A>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+17761A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,102 control chromosomes in the GnomAD database, including 38,762 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 0.71 (38762 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865
• Publications: 20 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=-0.9).
• 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+17761A>G		intron	N/A	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.-106+17652A>G		intron	N/A	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.-106+18060A>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+17761A>G		intron	N/A	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.-106+17761A>G		intron	N/A	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000901508.1		c.-106+18060A>G		intron	N/A	ENSP00000571567.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107570 AN: 151984 Hom.: 38725 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.708 AC: 107661 AN: 152102 Hom.: 38762 Cov.: 32 AF XY: 0.704 AC XY: 52354 AN XY: 74344

African (AFR) AF: 0.811 AC: 33626 AN: 41482

American (AMR) AF: 0.773 AC: 11823 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2208 AN: 3470

East Asian (EAS) AF: 0.874 AC: 4525 AN: 5180

South Asian (SAS) AF: 0.694 AC: 3350 AN: 4824

European-Finnish (FIN) AF: 0.536 AC: 5655 AN: 10542

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43994 AN: 67990

Other (OTH) AF: 0.721 AC: 1523 AN: 2112

Alfa AF: 0.661 Hom.: 14608

Bravo AF: 0.730

Asia WGS AF: 0.791 AC: 2747 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.74
PhyloP100		0.86
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: rs2179515; hg19: chr6-24628203;