6-24551396-A-G

Variant names:

• chr6-24551396-A-G
• rs2076313
• NM_014809.4:c.3040+38T>C

Variant summary

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

The NM_014809.4(KIAA0319):​c.3040+38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,425,996 control chromosomes in the GnomAD database, including 46,904 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 (7971 hom., cov: 31)
  • Exomes 𝑓: 0.24 (38933 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 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.3040+38T>C		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.3040+38T>C		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.3040+38T>C		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.3040+38T>C		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.2858-4053T>C		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.1273+38T>C		intron	N/A	ENSP00000483665.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45033 AN: 151894 Hom.: 7951 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.229 AC: 57277 AN: 250150 AF XY: 0.228

Gnomad AFR exome AF: 0.499

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.106

Gnomad FIN exome AF: 0.257

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.240 AC: 305305 AN: 1273984 Hom.: 38933 Cov.: 18 AF XY: 0.238 AC XY: 153445 AN XY: 643724

African (AFR) AF: 0.515 AC: 15334 AN: 29782

American (AMR) AF: 0.162 AC: 7215 AN: 44416

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5418 AN: 25158

East Asian (EAS) AF: 0.106 AC: 4108 AN: 38860

South Asian (SAS) AF: 0.241 AC: 19910 AN: 82596

European-Finnish (FIN) AF: 0.259 AC: 13800 AN: 53316

Middle Eastern (MID) AF: 0.324 AC: 1762 AN: 5446

European-Non Finnish (NFE) AF: 0.239 AC: 224534 AN: 940130

Other (OTH) AF: 0.244 AC: 13224 AN: 54280

GnomAD4 genome AF: 0.297 AC: 45088 AN: 152012 Hom.: 7971 Cov.: 31 AF XY: 0.294 AC XY: 21844 AN XY: 74296

African (AFR) AF: 0.497 AC: 20579 AN: 41424

American (AMR) AF: 0.207 AC: 3157 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3468

East Asian (EAS) AF: 0.109 AC: 567 AN: 5180

South Asian (SAS) AF: 0.223 AC: 1074 AN: 4822

European-Finnish (FIN) AF: 0.260 AC: 2749 AN: 10568

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15425 AN: 67960

Other (OTH) AF: 0.281 AC: 593 AN: 2112

Alfa AF: 0.265 Hom.: 1375

Bravo AF: 0.302

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.36
PhyloP100		-2.8
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: rs2076313; hg19: chr6-24551624; COSMIC: COSV65500124;