rs6935076

Variant names:

• chr6-24644094-C-T
• rs6935076
• NM_014809.4:c.-106+1642G>A

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+1642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,186 control chromosomes in the GnomAD database, including 7,232 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 0.30 (7232 hom., cov: 33)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 42 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 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.-106+1642G>A		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.-106+1533G>A		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.-106+1941G>A		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.-106+1642G>A		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.-106+1642G>A		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000535378.5	TSL:2	c.-224+1642G>A		intron	N/A	ENSP00000442403.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45665 AN: 152068 Hom.: 7232 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.300 AC: 45674 AN: 152186 Hom.: 7232 Cov.: 33 AF XY: 0.295 AC XY: 21972 AN XY: 74414

African (AFR) AF: 0.215 AC: 8938 AN: 41510

American (AMR) AF: 0.251 AC: 3847 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3472

East Asian (EAS) AF: 0.184 AC: 951 AN: 5174

South Asian (SAS) AF: 0.202 AC: 973 AN: 4828

European-Finnish (FIN) AF: 0.342 AC: 3623 AN: 10582

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25233 AN: 68004

Other (OTH) AF: 0.290 AC: 613 AN: 2114

Alfa AF: 0.335 Hom.: 1175

Bravo AF: 0.292

Asia WGS AF: 0.181 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.79
PhyloP100		-0.39
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: rs6935076; hg19: chr6-24644322;