Genetic Variant KIAA0319L:c.2779+56A>G (chr1-35442850-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024874.5(KIAA0319L):c.2779+56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,610,572 control chromosomes in the GnomAD database, including 37,155 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 0.26 ( 10563 hom., cov: 32)

Exomes 𝑓: 0.090 ( 26592 hom. )

Consequence

KIAA0319L
NM_024874.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.514

Publications

26 publications found

Variant links:

Genes affected

KIAA0319L (HGNC:30071): (KIAA0319 like) Predicted to act upstream of or within several processes, including flagellated sperm motility; proacrosomal vesicle fusion; and receptor-mediated endocytosis of virus by host cell. Located in Golgi apparatus; cytoplasmic vesicle; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

KIAA0319L Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

KIAA0319L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024874.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319L	NM_024874.5	MANE Select	c.2779+56A>G		intron	N/A	NP_079150.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIAA0319L	ENST00000325722.8	TSL:1 MANE Select	c.2779+56A>G	intron	N/A	ENSP00000318406.3	Q8IZA0-1
KIAA0319L	ENST00000930788.1		c.2953+56A>G	intron	N/A	ENSP00000600847.1
KIAA0319L	ENST00000961875.1		c.2908+56A>G	intron	N/A	ENSP00000631934.1

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39025

AN:

152072

Hom.:

10513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.610

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.776

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.0998

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0317

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.0903

AC:

131730

AN:

1458382

Hom.:

26592

AF XY:

0.0899

AC XY:

65270

AN XY:

725648

show subpopulations

African (AFR)

AF:

0.630

AC:

21019

AN:

33360

American (AMR)

AF:

0.387

AC:

17246

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.0451

AC:

1177

AN:

26072

East Asian (EAS)

AF:

0.789

AC:

31303

AN:

39660

South Asian (SAS)

AF:

0.194

AC:

16703

AN:

86100

European-Finnish (FIN)

AF:

0.0997

AC:

5314

AN:

53274

Middle Eastern (MID)

AF:

0.0738

AC:

413

AN:

5596

European-Non Finnish (NFE)

AF:

0.0274

AC:

30405

AN:

1109466

Other (OTH)

AF:

0.135

AC:

8150

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

3720

7440

11160

14880

18600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1894

3788

5682

7576

9470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.257

AC:

39141

AN:

152190

Hom.:

10563

Cov.:

AF XY:

0.263

AC XY:

19546

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.610

AC:

25318

AN:

41476

American (AMR)

AF:

0.318

AC:

4862

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3468

East Asian (EAS)

AF:

0.775

AC:

4015

AN:

5178

South Asian (SAS)

AF:

0.224

AC:

1082

AN:

4824

European-Finnish (FIN)

AF:

0.0998

AC:

1059

AN:

10608

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0317

AC:

2158

AN:

68026

Other (OTH)

AF:

0.226

AC:

477

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

941

1881

2822

3762

4703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.108

Hom.:

13031

Bravo

AF:

0.292

Asia WGS

AF:

0.499

AC:

1733

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.2

(source)

DANN

Benign

0.83

PhyloP100

-0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over