Variant 12-69348408-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000239.3(LYZ):c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 1,614,034 control chromosomes in the GnomAD database, including 1,989 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.063 ( 454 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1535 hom. )

Consequence

LYZ
NM_000239.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.641

Variant links:

Genes affected

LYZ (HGNC:6740): (lysozyme) This gene encodes human lysozyme, whose natural substrate is the bacterial cell wall peptidoglycan (cleaving the beta[1-4]glycosidic linkages between N-acetylmuramic acid and N-acetylglucosamine). Lysozyme is one of the antimicrobial agents found in human milk, and is also present in spleen, lung, kidney, white blood cells, plasma, saliva, and tears. The protein has antibacterial activity against a number of bacterial species. Missense mutations in this gene have been identified in heritable renal amyloidosis. [provided by RefSeq, Oct 2014]

LYZ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 12-69348408-C-T is Benign according to our data. Variant chr12-69348408-C-T is described in ClinVar as [Benign]. Clinvar id is 310329.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYZ	NM_000239.3 linkuse as main transcript	c.-1C>T		5_prime_UTR_variant	1/4	ENST00000261267.7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
LYZ	ENST00000261267.7 linkuse as main transcript	c.-1C>T	5_prime_UTR_variant	1/4	1	NM_000239.3	P1
LYZ	ENST00000548839.1 linkuse as main transcript	c.-1C>T	5_prime_UTR_variant	1/2	2
LYZ	ENST00000549690.1 linkuse as main transcript	c.-1C>T	5_prime_UTR_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0626

AC:

9529

AN:

152146

Hom.:

452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0471

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0422

Gnomad OTH

AF:

0.0554

GnomAD3 exomes

AF:

0.0387

AC:

9720

AN:

251468

Hom.:

325

AF XY:

0.0371

AC XY:

5049

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0276

Gnomad ASJ exome

AF:

0.0623

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0198

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.0427

Gnomad OTH exome

AF:

0.0399

GnomAD4 exome

AF:

0.0411

AC:

60119

AN:

1461770

Hom.:

1535

Cov.:

AF XY:

0.0404

AC XY:

29400

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.0302

Gnomad4 ASJ exome

AF:

0.0630

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0199

Gnomad4 FIN exome

AF:

0.0154

Gnomad4 NFE exome

AF:

0.0421

Gnomad4 OTH exome

AF:

0.0471

GnomAD4 genome

AF:

0.0626

AC:

9538

AN:

152264

Hom.:

454

Cov.:

AF XY:

0.0605

AC XY:

4503

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.0470

Gnomad4 ASJ

AF:

0.0579

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0159

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.0422

Gnomad4 OTH

AF:

0.0548

Alfa

AF:

0.0519

Hom.:

334

Bravo

AF:

0.0698

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0468

EpiControl

AF:

0.0469

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial visceral amyloidosis, Ostertag type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

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