NM_014809.4:c.1735-1191C>G

Variant names:

• chr6-24573889-G-C
• rs2744556
• NM_014809.4:c.1735-1191C>G

Variant summary

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

The NM_014809.4(KIAA0319):​c.1735-1191C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,884 control chromosomes in the GnomAD database, including 3,035 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 0.19 (3035 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 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.1735-1191C>G		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.1735-1191C>G		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.1735-1191C>G		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.1735-1191C>G		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.1735-1191C>G		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.7-1230C>G		intron	N/A	ENSP00000483665.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28915 AN: 151766 Hom.: 3028 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0834

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.191 AC: 28947 AN: 151884 Hom.: 3035 Cov.: 32 AF XY: 0.187 AC XY: 13865 AN XY: 74254

African (AFR) AF: 0.294 AC: 12183 AN: 41382

American (AMR) AF: 0.127 AC: 1940 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3472

East Asian (EAS) AF: 0.0836 AC: 431 AN: 5158

South Asian (SAS) AF: 0.184 AC: 885 AN: 4804

European-Finnish (FIN) AF: 0.128 AC: 1349 AN: 10550

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10977 AN: 67946

Other (OTH) AF: 0.183 AC: 387 AN: 2110

Alfa AF: 0.0726 Hom.: 92

Bravo AF: 0.195

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.48
DANN	Benign	0.49
PhyloP100		-0.61
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: rs2744556; hg19: chr6-24574117;