6-24544739-C-T

Variant names:

• chr6-24544739-C-T
• rs16889440
• NM_014809.4:c.*2426G>A

Variant summary

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

The NM_014809.4(KIAA0319):​c.*2426G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,152 control chromosomes in the GnomAD database, including 2,221 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 0.16 (2221 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: KIAA0319 NM_014809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.*2426G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214	c.*2426G>A		3_prime_UTR_variant	Exon 21 of 21	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24160 AN: 152026 Hom.: 2217 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.159 AC: 24175 AN: 152144 Hom.: 2221 Cov.: 32 AF XY: 0.158 AC XY: 11747 AN XY: 74392

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.0969

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.162

Alfa AF: 0.135 Hom.: 3328

Bravo AF: 0.164

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.59

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: rs16889440; hg19: chr6-24544967;