5-94384466-T-C

Variant names:

• chr5-94384466-T-C
• rs62364586
• NM_001145678.3:c.3620-8A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BS1 BS2

The NM_001145678.3(KIAA0825):​c.3620-8A>G variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.05135
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.57

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0825	NM_001145678.3	c.3620-8A>G		splice_region_variant, intron_variant	Intron 19 of 20	ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1	c.3620-8A>G		splice_region_variant, intron_variant	Intron 19 of 20		NM_001145678.3	ENSP00000506760.1
KIAA0825	ENST00000703867.1	c.3631-4A>G		splice_region_variant, intron_variant	Intron 19 of 20			ENSP00000515512.1
KIAA0825	ENST00000513200.7	c.3616-4A>G		splice_region_variant, intron_variant	Intron 18 of 19	5		ENSP00000424618.2

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2176 AN: 152092 Hom.: 22 Cov.: 32

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

GnomAD2 exomes AF: 0.0180 AC: 2833 AN: 157424 AF XY: 0.0194

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 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.: 28 AF XY: 0.0187 AC XY: 12883 AN XY: 688198

Gnomad4 AFR exome AF: 0.00304 AC: 96 AN: 31530

Gnomad4 AMR exome AF: 0.00902 AC: 322 AN: 35696

Gnomad4 ASJ exome AF: 0.0306 AC: 768 AN: 25128

Gnomad4 EAS exome AF: 0.0000280 AC: 1 AN: 35710

Gnomad4 SAS exome AF: 0.0270 AC: 2139 AN: 79150

Gnomad4 FIN exome AF: 0.0206 AC: 1018 AN: 49376

Gnomad4 NFE exome AF: 0.0183 AC: 19691 AN: 1074650

Gnomad4 Remaining exome AF: 0.0186 AC: 1076 AN: 57914

GnomAD4 genome AF: 0.0143 AC: 2177 AN: 152212 Hom.: 23 Cov.: 32 AF XY: 0.0142 AC XY: 1055 AN XY: 74400

Gnomad4 AFR AF: 0.00349 AC: 0.00349028 AN: 0.00349028

Gnomad4 AMR AF: 0.0103 AC: 0.0102735 AN: 0.0102735

Gnomad4 ASJ AF: 0.0294 AC: 0.0293948 AN: 0.0293948

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.0245 AC: 0.024461 AN: 0.024461

Gnomad4 FIN AF: 0.0212 AC: 0.0212264 AN: 0.0212264

Gnomad4 NFE AF: 0.0199 AC: 0.0199124 AN: 0.0199124

Gnomad4 OTH AF: 0.0161 AC: 0.0160681 AN: 0.0160681

Alfa AF: 0.0202 Hom.: 20

Bravo AF: 0.0134

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

KIAA0825-related disorder Benign:1

Nov 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	15
DANN	Benign	0.96
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs62364586; hg19: chr5-93720171; COSMIC: COSV107525716;