6-24540963-C-G

Variant names:

• chr6-24540963-C-G
• rs2760184
• ENST00000827594.1:n.429G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000827594.1(ENSG00000307634):​n.429G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 152,118 control chromosomes in the GnomAD database, including 297 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 0.056 (297 hom., cov: 32)
• Consequence: ENSG00000307634 ENST00000827594.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 3 publications found

Genes affected

ENSG00000307634 (HGNC:):

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	XM_047419602.1	c.*279G>C		3_prime_UTR_variant	Exon 21 of 21		XP_047275558.1
KIAA0319	XM_017011546.3	c.*279G>C		3_prime_UTR_variant	Exon 19 of 19		XP_016867035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000307634	ENST00000827594.1	n.429G>C		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8531 AN: 152000 Hom.: 296 Cov.: 32

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0376

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0489

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0561 AC: 8541 AN: 152118 Hom.: 297 Cov.: 32 AF XY: 0.0583 AC XY: 4333 AN XY: 74358

African (AFR) AF: 0.0747 AC: 3102 AN: 41522

American (AMR) AF: 0.0439 AC: 671 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3464

East Asian (EAS) AF: 0.00908 AC: 47 AN: 5178

South Asian (SAS) AF: 0.0374 AC: 180 AN: 4816

European-Finnish (FIN) AF: 0.135 AC: 1429 AN: 10556

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0431 AC: 2931 AN: 67992

Other (OTH) AF: 0.0479 AC: 101 AN: 2108

Alfa AF: 0.0216 Hom.: 9

Bravo AF: 0.0502

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2760184; hg19: chr6-24541191;