NM_014809.4:c.2734+212C>T

Variant names:

• chr6-24558801-G-A
• rs807540
• NM_014809.4:c.2734+212C>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.2734+212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,222 control chromosomes in the GnomAD database, including 60,600 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 0.89 (60600 hom., cov: 33)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2734+212C>T		intron_variant	Intron 17 of 20	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2734+212C>T		intron_variant	Intron 17 of 20	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134677 AN: 152104 Hom.: 60557 Cov.: 33

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.885 AC: 134772 AN: 152222 Hom.: 60600 Cov.: 33 AF XY: 0.879 AC XY: 65440 AN XY: 74426

African (AFR) AF: 0.935 AC: 38821 AN: 41526

American (AMR) AF: 0.731 AC: 11176 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3062 AN: 3470

East Asian (EAS) AF: 0.442 AC: 2285 AN: 5164

South Asian (SAS) AF: 0.851 AC: 4108 AN: 4828

European-Finnish (FIN) AF: 0.909 AC: 9637 AN: 10602

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.923 AC: 62773 AN: 68032

Other (OTH) AF: 0.871 AC: 1837 AN: 2110

Alfa AF: 0.908 Hom.: 8022

Bravo AF: 0.872

Asia WGS AF: 0.710 AC: 2471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.19
PhyloP100		0.27
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: rs807540; hg19: chr6-24559029;