Variant 1-201387170-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM1BP4_StrongBP6_Very_StrongBS2

The NM_005558.4(LAD1):c.191G>A(p.Ser64Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,508,558 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

LAD1
NM_005558.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.07

Variant links:

Genes affected

LAD1 (HGNC:6472): (ladinin 1) The protein encoded by this gene may be an anchoring filament that is a component of basement membranes. It may contribute to the stability of the association of the epithelial layers with the underlying mesenchyme. [provided by RefSeq, Jul 2008]

LAD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity LAD1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.006062001).

BP6

Variant 1-201387170-C-T is Benign according to our data. Variant chr1-201387170-C-T is described in ClinVar as [Benign]. Clinvar id is 771842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAD1	NM_005558.4 linkuse as main transcript	c.191G>A	p.Ser64Asn	missense_variant	3/10	ENST00000391967.7	NP_005549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAD1	ENST00000391967.7 linkuse as main transcript	c.191G>A	p.Ser64Asn	missense_variant	3/10	1	NM_005558.4	ENSP00000375829	P3

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00175

AC:

306

AN:

174476

Hom.:

AF XY:

0.00200

AC XY:

184

AN XY:

92116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00436

Gnomad FIN exome

AF:

0.000122

Gnomad NFE exome

AF:

0.00195

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00127

AC:

1716

AN:

1356322

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

916

AN XY:

663988

show subpopulations

Gnomad4 AFR exome

AF:

0.000233

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.0135

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00303

Gnomad4 FIN exome

AF:

0.000228

Gnomad4 NFE exome

AF:

0.000948

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.00123

AC:

188

AN:

152236

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.00128

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00192

AC:

230

Asia WGS

AF:

0.00289

AC:

AN:

3478

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	Aug 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.;.;T;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.0095

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.74

T;T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0061

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.5

M;.;.;.;.

MutationTaster

Benign

0.91

D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.2

N;N;.;.;.

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D;.;.;.

Sift4G

Uncertain

0.031

D;D;.;.;D

Polyphen

1.0

D;D;.;.;.

Vest4

0.33

MVP

0.10

MPC

0.50

ClinPred

0.14

GERP RS

4.9

Varity_R

0.27

gMVP

0.039

Splicing

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