6-24558291-A-T

Position:

• chr6-24558291-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014809.4(KIAA0319):​c.2734+722T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,312 control chromosomes in the GnomAD database, including 7,736 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 0.29 (7736 hom., cov: 30)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2734+722T>A		intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2734+722T>A		intron_variant		1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44077 AN: 151194 Hom.: 7718 Cov.: 30

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.292 AC: 44129 AN: 151312 Hom.: 7736 Cov.: 30 AF XY: 0.289 AC XY: 21370 AN XY: 73956

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.274

Alfa AF: 0.110 Hom.: 164

Bravo AF: 0.299

Asia WGS AF: 0.209 AC: 720 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs2760167; hg19: chr6-24558519;