rs2076313

chr6-24551396-A-G

Variant summary

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

The NM_014809.4(KIAA0319):c.3040+38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,425,996 control chromosomes in the GnomAD database, including 46,904 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 0.30 (7971 hom., cov: 31)
  • Exomes 𝑓: 0.24 (38933 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319	NM_014809.4	c.3040+38T>C		intron_variant		ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8	c.3040+38T>C		intron_variant		1	NM_014809.4	P2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45033 AN: 151894 Hom.: 7951 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.284

GnomAD3 exomes AF: 0.229 AC: 57277 AN: 250150 Hom.: 7464 AF XY: 0.228 AC XY: 30784 AN XY: 135178

Gnomad AFR exome AF: 0.499

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.241

Gnomad FIN exome AF: 0.257

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.240 AC: 305305 AN: 1273984 Hom.: 38933 Cov.: 18 AF XY: 0.238 AC XY: 153445 AN XY: 643724

Gnomad4 AFR exome AF: 0.515

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.297 AC: 45088 AN: 152012 Hom.: 7971 Cov.: 31 AF XY: 0.294 AC XY: 21844 AN XY: 74296

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.281

Alfa AF: 0.259 Hom.: 1282

Bravo AF: 0.302

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.18
Dann	Benign	0.36

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: rs2076313; hg19: chr6-24551624; COSMIC: COSV65500124;