chr6-24581055-G-A

Variant names:

• chr6-24581055-G-A
• rs807508
• NM_014809.4:c.1192-42C>T

Variant summary

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

The NM_014809.4(KIAA0319):​c.1192-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,256,466 control chromosomes in the GnomAD database, including 5,582 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 0.094 (687 hom., cov: 32)
  • Exomes 𝑓: 0.092 (4895 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 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.1192-42C>T		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.1192-42C>T		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.1192-42C>T		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.1192-42C>T		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.1192-42C>T		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.-537-42C>T		intron	N/A	ENSP00000483665.1

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14312 AN: 152088 Hom.: 686 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0851

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0901

Gnomad OTH AF: 0.0942

GnomAD2 exomes AF: 0.0911 AC: 22213 AN: 243846 AF XY: 0.0905

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.0898

Gnomad ASJ exome AF: 0.0775

Gnomad EAS exome AF: 0.0842

Gnomad FIN exome AF: 0.0732

Gnomad NFE exome AF: 0.0896

Gnomad OTH exome AF: 0.0944

GnomAD4 exome AF: 0.0917 AC: 101242 AN: 1104260 Hom.: 4895 Cov.: 15 AF XY: 0.0919 AC XY: 52006 AN XY: 566192

African (AFR) AF: 0.115 AC: 3023 AN: 26328

American (AMR) AF: 0.0897 AC: 3919 AN: 43674

Ashkenazi Jewish (ASJ) AF: 0.0780 AC: 1858 AN: 23828

East Asian (EAS) AF: 0.0573 AC: 2172 AN: 37928

South Asian (SAS) AF: 0.105 AC: 8315 AN: 78836

European-Finnish (FIN) AF: 0.0745 AC: 3774 AN: 50642

Middle Eastern (MID) AF: 0.0860 AC: 431 AN: 5014

European-Non Finnish (NFE) AF: 0.0923 AC: 72875 AN: 789264

Other (OTH) AF: 0.100 AC: 4875 AN: 48746

GnomAD4 genome AF: 0.0942 AC: 14339 AN: 152206 Hom.: 687 Cov.: 32 AF XY: 0.0923 AC XY: 6872 AN XY: 74416

African (AFR) AF: 0.113 AC: 4704 AN: 41490

American (AMR) AF: 0.0817 AC: 1250 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0851 AC: 295 AN: 3468

East Asian (EAS) AF: 0.0748 AC: 388 AN: 5186

South Asian (SAS) AF: 0.104 AC: 502 AN: 4822

European-Finnish (FIN) AF: 0.0715 AC: 758 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0901 AC: 6130 AN: 68020

Other (OTH) AF: 0.0951 AC: 201 AN: 2114

Alfa AF: 0.0899 Hom.: 939

Bravo AF: 0.0970

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.070
DANN	Benign	0.67
PhyloP100		-2.2
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: rs807508; hg19: chr6-24581283;