Variant 5-94384466-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_001145678.3(KIAA0825):c.3620-8A>G variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0178 in 1,547,060 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.014 ( 23 hom., cov: 32)

Exomes 𝑓: 0.018 ( 308 hom. )

Consequence

KIAA0825
NM_001145678.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.05135

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.57

Variant links:

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

KIAA0825 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 5-94384466-T-C is Benign according to our data. Variant chr5-94384466-T-C is described in ClinVar as [Benign]. Clinvar id is 3038019.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0143 (2177/152212) while in subpopulation SAS AF= 0.0245 (118/4824). AF 95% confidence interval is 0.0209. There are 23 homozygotes in gnomad4. There are 1055 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0825	NM_001145678.3 linkuse as main transcript	c.3620-8A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1 linkuse as main transcript	c.3620-8A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NM_001145678.3	ENSP00000506760	A1
KIAA0825	ENST00000513200.7 linkuse as main transcript	c.3616-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000424618	A1	Q8IV33-1
KIAA0825	ENST00000703867.1 linkuse as main transcript	c.3631-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			ENSP00000515512	P4

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2176

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00350

Gnomad AMI

AF:

0.0374

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0212

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0162

GnomAD3 exomes

AF:

0.0180

AC:

2833

AN:

157424

Hom.:

AF XY:

0.0194

AC XY:

1609

AN XY:

83128

show subpopulations

Gnomad AFR exome

AF:

0.00306

Gnomad AMR exome

AF:

0.00826

Gnomad ASJ exome

AF:

0.0324

Gnomad EAS exome

AF:

0.0000917

Gnomad SAS exome

AF:

0.0260

Gnomad FIN exome

AF:

0.0205

Gnomad NFE exome

AF:

0.0212

Gnomad OTH exome

AF:

0.0207

GnomAD4 exome

AF:

0.0181

AC:

25288

AN:

1394848

Hom.:

308

Cov.:

AF XY:

0.0187

AC XY:

12883

AN XY:

688198

show subpopulations

Gnomad4 AFR exome

AF:

0.00304

Gnomad4 AMR exome

AF:

0.00902

Gnomad4 ASJ exome

AF:

0.0306

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0270

Gnomad4 FIN exome

AF:

0.0206

Gnomad4 NFE exome

AF:

0.0183

Gnomad4 OTH exome

AF:

0.0186

GnomAD4 genome

AF:

0.0143

AC:

2177

AN:

152212

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1055

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00349

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0245

Gnomad4 FIN

AF:

0.0212

Gnomad4 NFE

AF:

0.0199

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0192

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIAA0825-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.051

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over