Variant 11-111544009-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_178834.5(LAYN):c.172G>A(p.Glu58Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,614,176 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 42 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 40 hom. )

Consequence

LAYN
NM_178834.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

LAYN (HGNC:29471): (layilin) Enables hyaluronic acid binding activity. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

LAYN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010390997).

BP6

Variant 11-111544009-G-A is Benign according to our data. Variant chr11-111544009-G-A is described in ClinVar as [Benign]. Clinvar id is 776657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1734/152312) while in subpopulation AFR AF= 0.0393 (1632/41550). AF 95% confidence interval is 0.0377. There are 42 homozygotes in gnomad4. There are 839 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAYN	NM_178834.5 link	c.172G>A	p.Glu58Lys	missense_variant	2/7	ENST00000375614.7	NP_849156.1	Q6UX15-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAYN	ENST00000375614.7 link	c.172G>A	p.Glu58Lys	missense_variant	2/7	1	NM_178834.5	ENSP00000364764.2		Q6UX15-2

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1717

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0390

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00281

AC:

706

AN:

251422

Hom.:

AF XY:

0.00210

AC XY:

286

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0377

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00123

AC:

1801

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

796

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0420

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.00275

GnomAD4 genome

AF:

0.0114

AC:

1734

AN:

152312

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

839

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0393

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00237

Hom.:

Bravo

AF:

0.0132

ESP6500AA

AF:

0.0368

AC:

162

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00362

AC:

439

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.036

.;T;T;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

T;T;D;T

MetaRNN

Benign

0.010

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.2

.;M;.;.

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0070

D;D;D;D

Sift4G

Uncertain

0.021

D;D;D;D

Polyphen

0.60

P;D;D;D

Vest4

0.50

MVP

0.67

MPC

0.46

ClinPred

0.021

GERP RS

4.5

Varity_R

0.64

gMVP

0.75

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