chr5-94386345-G-T

Variant names:

• chr5-94386345-G-T
• rs29913
• NM_001145678.3:c.3516C>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001145678.3(KIAA0825):​c.3516C>A​(p.Ile1172Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,550,736 control chromosomes in the GnomAD database, including 17,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (1472 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15946 hom.)
• Consequence: KIAA0825 NM_001145678.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.526

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 5-94386345-G-T is Benign according to our data. Variant chr5-94386345-G-T is described in ClinVar as [Benign]. Clinvar id is 3057167.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.526 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0825	NM_001145678.3	c.3516C>A	p.Ile1172Ile	synonymous_variant	Exon 19 of 21	ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1	c.3516C>A	p.Ile1172Ile	synonymous_variant	Exon 19 of 21		NM_001145678.3	ENSP00000506760.1
KIAA0825	ENST00000703867.1	c.3531C>A	p.Ile1177Ile	synonymous_variant	Exon 19 of 21			ENSP00000515512.1
KIAA0825	ENST00000513200.7	c.3516C>A	p.Ile1172Ile	synonymous_variant	Exon 18 of 20	5		ENSP00000424618.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20392 AN: 152032 Hom.: 1472 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.130 AC: 20521 AN: 157864 Hom.: 1551 AF XY: 0.136 AC XY: 11333 AN XY: 83314

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.0753

Gnomad ASJ exome AF: 0.176

Gnomad EAS exome AF: 0.000367

Gnomad SAS exome AF: 0.182

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.146 AC: 204286 AN: 1398586 Hom.: 15946 Cov.: 31 AF XY: 0.148 AC XY: 101825 AN XY: 689786

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.0794

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.000588

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.134 AC: 20410 AN: 152150 Hom.: 1472 Cov.: 32 AF XY: 0.131 AC XY: 9731 AN XY: 74384

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0985

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.122

Alfa AF: 0.147 Hom.: 4118

Bravo AF: 0.130

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

KIAA0825-related disorder Benign:1

Nov 19, 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	-0.67
CADD	Benign	2.2
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs29913; hg19: chr5-93722050; COSMIC: COSV70248983;