1-201386371-C-T

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

2

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]

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
LAD1NM_005558.4 linkc.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
LAD1ENST00000391967.7 linkc.990G>A p.Pro330Pro synonymous_variant Exon 3 of 10 1 NM_005558.4 ENSP00000375829.2 O00515
LAD1ENST00000367313.4 linkc.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.:
11
Cov.:
33
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.:
9
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.:
39
Cov.:
45
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.:
11
Cov.:
33
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.:
1
Bravo
AF:
0.00526
Asia WGS
AF:
0.00318
AC:
11
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.

Other links and lift over

dbSNP: rs141517560; hg19: chr1-201355499; API