Variant 1-201386770-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005558.4(LAD1):c.591C>T(p.Ser197Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,614,120 control chromosomes in the GnomAD database, including 316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 175 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 141 hom. )

Consequence

LAD1
NM_005558.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.14

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-201386770-G-A is Benign according to our data. Variant chr1-201386770-G-A is described in ClinVar as [Benign]. Clinvar id is 767741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAD1	NM_005558.4 linkuse as main transcript	c.591C>T	p.Ser197Ser	synonymous_variant	3/10	ENST00000391967.7	NP_005549.2	O00515

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAD1	ENST00000391967.7 linkuse as main transcript	c.591C>T	p.Ser197Ser	synonymous_variant	3/10	1	NM_005558.4	ENSP00000375829.2	O00515
LAD1	ENST00000367313.4 linkuse as main transcript	c.633C>T	p.Ser211Ser	synonymous_variant	3/10	1		ENSP00000356282.3	E9PDI4
LAD1	ENST00000631576.1 linkuse as main transcript	c.*41C>T		downstream_gene_variant		4		ENSP00000488829.1	A0A0J9YYF6

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3881

AN:

152132

Hom.:

168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0891

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00877

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00673

AC:

1691

AN:

251406

Hom.:

AF XY:

0.00515

AC XY:

700

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0899

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000369

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00275

AC:

4023

AN:

1461870

Hom.:

141

Cov.:

AF XY:

0.00239

AC XY:

1737

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0896

Gnomad4 AMR exome

AF:

0.00499

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000324

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.0257

AC:

3910

AN:

152250

Hom.:

175

Cov.:

AF XY:

0.0256

AC XY:

1905

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0895

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0137

Hom.:

Bravo

AF:

0.0297

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000652

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	Apr 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.11

DANN

Benign

0.42

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