chr6-24549678-C-G

Variant names:

• chr6-24549678-C-G
• rs807533
• NM_014809.4:c.3040+1756G>C

Variant summary

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

The NM_014809.4(KIAA0319):​c.3040+1756G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,098 control chromosomes in the GnomAD database, including 27,984 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 0.58 (27984 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.3040+1756G>C		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.3040+1756G>C		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.3040+1756G>C		intron	N/A	NP_001337332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.3040+1756G>C		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.2858-2335G>C		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.1273+1756G>C		intron	N/A	ENSP00000483665.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88939 AN: 151980 Hom.: 27980 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.824

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.585 AC: 88965 AN: 152098 Hom.: 27984 Cov.: 32 AF XY: 0.582 AC XY: 43246 AN XY: 74324

African (AFR) AF: 0.374 AC: 15534 AN: 41502

American (AMR) AF: 0.515 AC: 7870 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2387 AN: 3470

East Asian (EAS) AF: 0.363 AC: 1872 AN: 5162

South Asian (SAS) AF: 0.648 AC: 3124 AN: 4818

European-Finnish (FIN) AF: 0.670 AC: 7070 AN: 10554

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48971 AN: 68002

Other (OTH) AF: 0.577 AC: 1216 AN: 2106

Alfa AF: 0.654 Hom.: 4226

Bravo AF: 0.562

Asia WGS AF: 0.515 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.72
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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: rs807533; hg19: chr6-24549906;