rs2760157

Positions:

• chr6-24578044-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.1505+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,492,276 control chromosomes in the GnomAD database, including 40,997 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 0.28 (7089 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33908 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.1505+66C>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.1505+66C>T		intron_variant		1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42766 AN: 151776 Hom.: 7071 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.210 AC: 280928 AN: 1340382 Hom.: 33908 AF XY: 0.207 AC XY: 136884 AN XY: 662550

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.282 AC: 42840 AN: 151894 Hom.: 7089 Cov.: 32 AF XY: 0.286 AC XY: 21202 AN XY: 74204

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.255

Alfa AF: 0.196 Hom.: 3274

Bravo AF: 0.297

Asia WGS AF: 0.324 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.97
DANN	Benign	0.54

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: rs2760157; hg19: chr6-24578272; COSMIC: COSV65497154;