6-24550765-C-T

Variant names:

• chr6-24550765-C-T
• rs2760179
• NM_014809.4:c.3040+669G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014809.4(KIAA0319):​c.3040+669G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00567 in 151,798 control chromosomes in the GnomAD database, including 36 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 0.0057 (36 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00567 (860/151798) while in subpopulation AMR AF = 0.0517 (788/15252). AF 95% confidence interval is 0.0487. There are 36 homozygotes in GnomAd4. There are 496 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.3040+669G>A		intron_variant	Intron 20 of 20	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.3040+669G>A		intron_variant	Intron 20 of 20	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.00562 AC: 853 AN: 151678 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.000267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.0000953

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00335

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

GnomAD4 genome AF: 0.00567 AC: 860 AN: 151798 Hom.: 36 Cov.: 32 AF XY: 0.00669 AC XY: 496 AN XY: 74172

African (AFR) AF: 0.000266 AC: 11 AN: 41378

American (AMR) AF: 0.0517 AC: 788 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5162

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4812

European-Finnish (FIN) AF: 0.0000953 AC: 1 AN: 10488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67918

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.0000816 Hom.: 294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.084
DANN	Benign	0.93
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2760179; hg19: chr6-24550993;