6-24545368-A-C

Position:

• chr6-24545368-A-C

Variant summary

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

The NM_014809.4(KIAA0319):​c.*1797T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 152,176 control chromosomes in the GnomAD database, including 694 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 0.080 (694 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: KIAA0319 NM_014809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319	NM_014809.4	c.*1797T>G		3_prime_UTR_variant	21/21	ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8	c.*1797T>G		3_prime_UTR_variant	21/21	1	NM_014809.4	P2

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12148 AN: 152054 Hom.: 691 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0542

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.0735

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0799 AC: 12161 AN: 152172 Hom.: 694 Cov.: 32 AF XY: 0.0815 AC XY: 6060 AN XY: 74398

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0542

Gnomad4 ASJ AF: 0.0214

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0435

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0572 Hom.: 127

Bravo AF: 0.0778

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
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: rs2817243; hg19: chr6-24545596;