chr6-24547378-G-A

Position:

• chr6-24547378-G-A

Variant summary

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

The NM_014809.4(KIAA0319):​c.3041-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,579,254 control chromosomes in the GnomAD database, including 28,854 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 0.23 (4698 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24156 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.3041-35C>T		intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.3041-35C>T		intron_variant		1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34831 AN: 152016 Hom.: 4676 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.232

GnomAD3 exomes AF: 0.188 AC: 43143 AN: 229864 Hom.: 4441 AF XY: 0.188 AC XY: 23316 AN XY: 124214

Gnomad AFR exome AF: 0.372

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.212

Gnomad FIN exome AF: 0.233

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.179 AC: 255581 AN: 1427118 Hom.: 24156 Cov.: 25 AF XY: 0.179 AC XY: 127241 AN XY: 709208

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.0924

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.229 AC: 34887 AN: 152136 Hom.: 4698 Cov.: 32 AF XY: 0.231 AC XY: 17171 AN XY: 74368

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.229

Alfa AF: 0.186 Hom.: 2229

Bravo AF: 0.231

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.70

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: rs2817245; hg19: chr6-24547606;