rs2745333

Variant names:

• chr6-24617969-A-G
• rs2745333
• NM_014809.4:c.-105-16761T>C

Variant summary

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

The NM_014809.4(KIAA0319):​c.-105-16761T>C 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 151,894 control chromosomes in the GnomAD database, including 39,601 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 (39601 hom., cov: 30)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.-105-16761T>C		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.-105-16761T>C		intron_variant	Intron 1 of 20	1	NM_014809.4	ENSP00000367459.3
KIAA0319	ENST00000537886.5	c.-105-16761T>C		intron_variant	Intron 1 of 18	1		ENSP00000439700.1
KIAA0319	ENST00000535378.5	c.-223-16761T>C		intron_variant	Intron 1 of 21	2		ENSP00000442403.1
KIAA0319	ENST00000430948.6	c.-80-21351T>C		intron_variant	Intron 1 of 19	2		ENSP00000401086.2

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107004 AN: 151776 Hom.: 39546 Cov.: 30

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.705 AC: 107115 AN: 151894 Hom.: 39601 Cov.: 30 AF XY: 0.701 AC XY: 52020 AN XY: 74238

African (AFR) AF: 0.915 AC: 37902 AN: 41422

American (AMR) AF: 0.754 AC: 11509 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2172 AN: 3468

East Asian (EAS) AF: 0.879 AC: 4540 AN: 5164

South Asian (SAS) AF: 0.740 AC: 3555 AN: 4802

European-Finnish (FIN) AF: 0.480 AC: 5048 AN: 10526

Middle Eastern (MID) AF: 0.767 AC: 224 AN: 292

European-Non Finnish (NFE) AF: 0.588 AC: 39949 AN: 67942

Other (OTH) AF: 0.728 AC: 1535 AN: 2108

Alfa AF: 0.643 Hom.: 4019

Bravo AF: 0.737

Asia WGS AF: 0.811 AC: 2821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.28
PhyloP100		-0.58
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: rs2745333; hg19: chr6-24618197;