rs4472344

Variant names:

• chr6-24601012-G-A
• rs4472344
• NM_014809.4:c.55+37C>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.55+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 1,613,516 control chromosomes in the GnomAD database, including 800 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 0.038 (213 hom., cov: 31)
  • Exomes 𝑓: 0.022 (587 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.55+37C>T		intron_variant	Intron 2 of 20	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.55+37C>T		intron_variant	Intron 2 of 20	1	NM_014809.4	ENSP00000367459.3
KIAA0319	ENST00000537886.5	c.55+37C>T		intron_variant	Intron 2 of 18	1		ENSP00000439700.1
KIAA0319	ENST00000535378.5	c.-64+37C>T		intron_variant	Intron 2 of 21	2		ENSP00000442403.1
KIAA0319	ENST00000430948.6	c.-80-4394C>T		intron_variant	Intron 1 of 19	2		ENSP00000401086.2

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5796 AN: 151996 Hom.: 212 Cov.: 31

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0346

GnomAD2 exomes AF: 0.0180 AC: 4518 AN: 251082 AF XY: 0.0160

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.00198

Gnomad EAS exome AF: 0.00103

Gnomad FIN exome AF: 0.00337

Gnomad NFE exome AF: 0.0199

Gnomad OTH exome AF: 0.0144

GnomAD4 exome AF: 0.0224 AC: 32683 AN: 1461402 Hom.: 587 Cov.: 31 AF XY: 0.0212 AC XY: 15422 AN XY: 727024

African (AFR) AF: 0.0996 AC: 3331 AN: 33460

American (AMR) AF: 0.0123 AC: 552 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00237 AC: 62 AN: 26134

East Asian (EAS) AF: 0.000630 AC: 25 AN: 39698

South Asian (SAS) AF: 0.000939 AC: 81 AN: 86218

European-Finnish (FIN) AF: 0.00343 AC: 183 AN: 53416

Middle Eastern (MID) AF: 0.00712 AC: 41 AN: 5762

European-Non Finnish (NFE) AF: 0.0243 AC: 27051 AN: 1111634

Other (OTH) AF: 0.0225 AC: 1357 AN: 60372

GnomAD4 genome AF: 0.0381 AC: 5799 AN: 152114 Hom.: 213 Cov.: 31 AF XY: 0.0354 AC XY: 2632 AN XY: 74354

African (AFR) AF: 0.0961 AC: 3984 AN: 41446

American (AMR) AF: 0.0181 AC: 277 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4814

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0207 AC: 1410 AN: 68012

Other (OTH) AF: 0.0343 AC: 72 AN: 2102

Alfa AF: 0.0280 Hom.: 40

Bravo AF: 0.0426

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.34
PhyloP100		1.5
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: rs4472344; hg19: chr6-24601240;