rs6456624

Variant names:

• chr6-24638995-T-C
• rs6456624
• NM_014809.4:c.-106+6741A>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.-106+6741A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,090 control chromosomes in the GnomAD database, including 35,382 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 0.68 (35382 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.-106+6741A>G		intron_variant	Intron 1 of 20	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.-106+6741A>G		intron_variant	Intron 1 of 20	1	NM_014809.4	ENSP00000367459.3
KIAA0319	ENST00000537886.5	c.-106+6741A>G		intron_variant	Intron 1 of 18	1		ENSP00000439700.1
KIAA0319	ENST00000535378.5	c.-224+6741A>G		intron_variant	Intron 1 of 21	2		ENSP00000442403.1
KIAA0319	ENST00000430948.6	c.-81+6632A>G		intron_variant	Intron 1 of 19	2		ENSP00000401086.2

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102586 AN: 151972 Hom.: 35350 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.675 AC: 102669 AN: 152090 Hom.: 35382 Cov.: 32 AF XY: 0.672 AC XY: 49926 AN XY: 74334

African (AFR) AF: 0.782 AC: 32450 AN: 41470

American (AMR) AF: 0.740 AC: 11310 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2116 AN: 3472

East Asian (EAS) AF: 0.872 AC: 4518 AN: 5180

South Asian (SAS) AF: 0.677 AC: 3257 AN: 4814

European-Finnish (FIN) AF: 0.491 AC: 5182 AN: 10564

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41443 AN: 67992

Other (OTH) AF: 0.684 AC: 1446 AN: 2114

Alfa AF: 0.638 Hom.: 3888

Bravo AF: 0.699

Asia WGS AF: 0.781 AC: 2713 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.47
PhyloP100		0.26
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: rs6456624; hg19: chr6-24639223;