chr6-24644967-G-C

Variant names:

• chr6-24644967-G-C
• rs2328846
• NM_014809.4:c.-106+769C>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+769C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,040 control chromosomes in the GnomAD database, including 38,136 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 (38136 hom., cov: 33)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.-106+769C>G		intron_variant	Intron 1 of 20	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.-106+769C>G		intron_variant	Intron 1 of 20	1	NM_014809.4	ENSP00000367459.3
KIAA0319	ENST00000537886.5	c.-106+769C>G		intron_variant	Intron 1 of 18	1		ENSP00000439700.1
KIAA0319	ENST00000535378.5	c.-224+769C>G		intron_variant	Intron 1 of 21	2		ENSP00000442403.1
KIAA0319	ENST00000430948.6	c.-81+660C>G		intron_variant	Intron 1 of 19	2		ENSP00000401086.2

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106814 AN: 151922 Hom.: 38108 Cov.: 33

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.703 AC: 106893 AN: 152040 Hom.: 38136 Cov.: 33 AF XY: 0.700 AC XY: 51974 AN XY: 74292

African (AFR) AF: 0.796 AC: 33018 AN: 41496

American (AMR) AF: 0.767 AC: 11717 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2162 AN: 3468

East Asian (EAS) AF: 0.873 AC: 4524 AN: 5180

South Asian (SAS) AF: 0.696 AC: 3356 AN: 4820

European-Finnish (FIN) AF: 0.539 AC: 5671 AN: 10512

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

European-Non Finnish (NFE) AF: 0.647 AC: 43987 AN: 67970

Other (OTH) AF: 0.712 AC: 1502 AN: 2110

Alfa AF: 0.664 Hom.: 3962

Bravo AF: 0.724

Asia WGS AF: 0.792 AC: 2746 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.2
DANN	Benign	0.64
PhyloP100		0.42
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: rs2328846; hg19: chr6-24645195;