rs7770041

Positions:

• chr6-24547123-T-C

Variant summary

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

The NM_014809.4(KIAA0319):​c.*42A>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 0.0241 in 1,603,148 control chromosomes in the GnomAD database, including 868 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 0.041 (267 hom., cov: 33)
  • Exomes 𝑓: 0.022 (601 hom.)
• Consequence: KIAA0319 NM_014809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.*42A>G		3_prime_UTR_variant	21/21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214	c.*42A>G		3_prime_UTR_variant	21/21	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6224 AN: 152200 Hom.: 264 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0320

GnomAD3 exomes AF: 0.0186 AC: 4647 AN: 249378 Hom.: 142 AF XY: 0.0163 AC XY: 2190 AN XY: 134682

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.00172

Gnomad EAS exome AF: 0.000870

Gnomad SAS exome AF: 0.00166

Gnomad FIN exome AF: 0.00337

Gnomad NFE exome AF: 0.0198

Gnomad OTH exome AF: 0.0131

GnomAD4 exome AF: 0.0224 AC: 32453 AN: 1450830 Hom.: 601 Cov.: 28 AF XY: 0.0213 AC XY: 15417 AN XY: 722122

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0117

Gnomad4 ASJ exome AF: 0.00174

Gnomad4 EAS exome AF: 0.000505

Gnomad4 SAS exome AF: 0.00203

Gnomad4 FIN exome AF: 0.00345

Gnomad4 NFE exome AF: 0.0238

Gnomad4 OTH exome AF: 0.0237

GnomAD4 genome AF: 0.0409 AC: 6234 AN: 152318 Hom.: 267 Cov.: 33 AF XY: 0.0381 AC XY: 2835 AN XY: 74476

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0182

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0239 Hom.: 93

Bravo AF: 0.0454

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.86

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: rs7770041; hg19: chr6-24547351;