Genetic Variant NM_178834.5:c.40G>A (chr11-111540883-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178834.5(LAYN):c.40G>A(p.Val14Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00984 in 1,532,362 control chromosomes in the GnomAD database, including 1,179 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 618 hom., cov: 33)

Exomes 𝑓: 0.0055 ( 561 hom. )

Consequence

LAYN
NM_178834.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.214

Publications

8 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012070537).

BP6

Variant 11-111540883-G-A is Benign according to our data. Variant chr11-111540883-G-A is described in ClinVar as Benign. ClinVar VariationId is 768483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAYN	NM_178834.5 link	c.40G>A	p.Val14Met	missense_variant	Exon 1 of 7	ENST00000375614.7	NP_849156.1	Q6UX15-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAYN	ENST00000375614.7 link	c.40G>A	p.Val14Met	missense_variant	Exon 1 of 7	1	NM_178834.5	ENSP00000364764.2		Q6UX15-2

Frequencies

GnomAD3 genomes

AF:

0.0490

AC:

7462

AN:

152198

Hom.:

615

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0193

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.0349

GnomAD2 exomes

AF:

0.0109

AC:

1405

AN:

128318

AF XY:

0.00840

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.00732

Gnomad ASJ exome

AF:

0.00623

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000178

Gnomad NFE exome

AF:

0.000972

Gnomad OTH exome

AF:

0.00726

GnomAD4 exome

AF:

0.00550

AC:

7584

AN:

1380056

Hom.:

561

Cov.:

AF XY:

0.00477

AC XY:

3251

AN XY:

680954

show subpopulations

African (AFR)

AF:

0.177

AC:

5544

AN:

31392

American (AMR)

AF:

0.00924

AC:

329

AN:

35598

Ashkenazi Jewish (ASJ)

AF:

0.00447

AC:

112

AN:

25072

East Asian (EAS)

AF:

0.00

AC:

AN:

35624

South Asian (SAS)

AF:

0.000481

AC:

AN:

78992

European-Finnish (FIN)

AF:

0.000414

AC:

AN:

33788

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

4302

European-Non Finnish (NFE)

AF:

0.000706

AC:

761

AN:

1077664

Other (OTH)

AF:

0.0127

AC:

731

AN:

57624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

357

714

1071

1428

1785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0492

AC:

7490

AN:

152306

Hom.:

618

Cov.:

AF XY:

0.0477

AC XY:

3553

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.169

AC:

7024

AN:

41558

American (AMR)

AF:

0.0192

AC:

294

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00103

AC:

AN:

68030

Other (OTH)

AF:

0.0346

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

326

652

979

1305

1631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0359

Hom.:

Bravo

AF:

0.0559

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.0101

AC:

230

Asia WGS

AF:

0.0110

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.1

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0083

.;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.43

T;T;T;T

MetaRNN

Benign

0.0012

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

L;L;.;.

PhyloP100

-0.21

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.25

N;N;N;N

REVEL

Benign

0.024

Sift

Benign

0.14

T;T;T;T

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.0070

B;B;B;B

Vest4

0.077

MPC

0.082

ClinPred

0.0023

GERP RS

-0.90

PromoterAI

0.064

Neutral

(source)

Varity_R

0.036

gMVP

0.48

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over