6-24579957-CAA-CAAA

Variant names:

• chr6-24579957-C-CA
• rs3215493
• NM_014809.4:c.1280-8dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014809.4(KIAA0319):​c.1280-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,565,220 control chromosomes in the GnomAD database, including 29,274 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3775 hom., cov: 26)
  • Exomes 𝑓: 0.18 (25499 hom.)
• Consequence: KIAA0319 NM_014809.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.1280-8dupT		splice_region_variant, intron_variant	Intron 7 of 20	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.1280-8_1280-7insT		splice_region_variant, intron_variant	Intron 7 of 20	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31125 AN: 151486 Hom.: 3772 Cov.: 26

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0914

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.194

GnomAD2 exomes AF: 0.234 AC: 42833 AN: 182878 AF XY: 0.223

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.413

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.501

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.180 AC: 253926 AN: 1413616 Hom.: 25499 Cov.: 28 AF XY: 0.178 AC XY: 124564 AN XY: 700344

African (AFR) AF: 0.197 AC: 6290 AN: 31918

American (AMR) AF: 0.391 AC: 15021 AN: 38388

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 4060 AN: 25234

East Asian (EAS) AF: 0.525 AC: 19560 AN: 37232

South Asian (SAS) AF: 0.167 AC: 13510 AN: 80678

European-Finnish (FIN) AF: 0.245 AC: 12490 AN: 51058

Middle Eastern (MID) AF: 0.143 AC: 809 AN: 5668

European-Non Finnish (NFE) AF: 0.158 AC: 171124 AN: 1085002

Other (OTH) AF: 0.189 AC: 11062 AN: 58438

GnomAD4 genome AF: 0.206 AC: 31159 AN: 151604 Hom.: 3775 Cov.: 26 AF XY: 0.213 AC XY: 15739 AN XY: 74050

African (AFR) AF: 0.195 AC: 8053 AN: 41372

American (AMR) AF: 0.322 AC: 4899 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 563 AN: 3462

East Asian (EAS) AF: 0.530 AC: 2729 AN: 5150

South Asian (SAS) AF: 0.190 AC: 912 AN: 4800

European-Finnish (FIN) AF: 0.256 AC: 2679 AN: 10448

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10779 AN: 67850

Other (OTH) AF: 0.194 AC: 409 AN: 2106

Alfa AF: 0.109 Hom.: 218

Bravo AF: 0.209

Asia WGS AF: 0.308 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3215493; hg19: chr6-24580185; COSMIC: COSV107486685;