Genetic Variant LAD1:p.Pro330Pro (chr1-201386371-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005558.4(LAD1):c.990G>A(p.Pro330Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00379 in 1,504,662 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 11 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 39 hom. )

Consequence

LAD1
NM_005558.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.715

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=-0.65).

BP6

Variant 1-201386371-C-T is Benign according to our data. Variant chr1-201386371-C-T is described in ClinVar as [Benign]. Clinvar id is 791519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.715 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00369 (4997/1352398) while in subpopulation MID AF= 0.0287 (144/5026). AF 95% confidence interval is 0.0248. There are 39 homozygotes in gnomad4_exome. There are 2538 alleles in male gnomad4_exome subpopulation. Median coverage is 45. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAD1	NM_005558.4 link	c.990G>A	p.Pro330Pro	synonymous_variant	Exon 3 of 10	ENST00000391967.7	NP_005549.2	O00515

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAD1	ENST00000391967.7 link	c.990G>A	p.Pro330Pro	synonymous_variant	Exon 3 of 10	1	NM_005558.4	ENSP00000375829.2		O00515
LAD1	ENST00000367313.4 link	c.1032G>A	p.Pro344Pro	synonymous_variant	Exon 3 of 10	1		ENSP00000356282.3		E9PDI4

Frequencies

GnomAD3 genomes

AF:

0.00462

AC:

703

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00360

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00337

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00414

AC:

638

AN:

154034

Hom.:

AF XY:

0.00396

AC XY:

321

AN XY:

81088

show subpopulations

Gnomad AFR exome

AF:

0.00342

Gnomad AMR exome

AF:

0.00354

Gnomad ASJ exome

AF:

0.0482

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00408

Gnomad OTH exome

AF:

0.00666

GnomAD4 exome

AF:

0.00369

AC:

4997

AN:

1352398

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

2538

AN XY:

661336

show subpopulations

Gnomad4 AFR exome

AF:

0.00356

Gnomad4 AMR exome

AF:

0.00514

Gnomad4 ASJ exome

AF:

0.0522

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00538

Gnomad4 FIN exome

AF:

0.000632

Gnomad4 NFE exome

AF:

0.00258

Gnomad4 OTH exome

AF:

0.00815

GnomAD4 genome

AF:

0.00459

AC:

699

AN:

152264

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

317

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00358

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.0576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00337

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00477

Hom.:

Bravo

AF:

0.00526

Asia WGS

AF:

0.00318

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.38

DANN

Benign

0.32

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