Genetic Variant LAMA5:c.568+122G>A (chr20-62353012-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005560.6(LAMA5):c.568+122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 690,182 control chromosomes in the GnomAD database, including 1,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 412 hom., cov: 33)

Exomes 𝑓: 0.064 ( 1500 hom. )

Consequence

LAMA5
NM_005560.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.04

Variant links:

Genes affected

LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]

LAMA5 links:

LAMA5-AS1 (HGNC:40334): (LAMA5 antisense RNA 1)

LAMA5-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 20-62353012-C-T is Benign according to our data. Variant chr20-62353012-C-T is described in ClinVar as [Benign]. Clinvar id is 1225849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA5	NM_005560.6 link	c.568+122G>A		intron_variant	Intron 3 of 79	ENST00000252999.7	NP_005551.3	O15230-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA5	ENST00000252999.7 link	c.568+122G>A		intron_variant	Intron 3 of 79	1	NM_005560.6	ENSP00000252999.3		O15230-1

Frequencies

GnomAD3 genomes

AF:

0.0691

AC:

10518

AN:

152136

Hom.:

412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0935

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0462

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.0187

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.0959

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0554

Gnomad OTH

AF:

0.0478

GnomAD4 exome

AF:

0.0642

AC:

34542

AN:

537928

Hom.:

1500

Cov.:

AF XY:

0.0683

AC XY:

19101

AN XY:

279738

show subpopulations

Gnomad4 AFR exome

AF:

0.0947

Gnomad4 AMR exome

AF:

0.0313

Gnomad4 ASJ exome

AF:

0.0331

Gnomad4 EAS exome

AF:

0.0149

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.0918

Gnomad4 NFE exome

AF:

0.0548

Gnomad4 OTH exome

AF:

0.0562

GnomAD4 genome

AF:

0.0692

AC:

10533

AN:

152254

Hom.:

412

Cov.:

AF XY:

0.0725

AC XY:

5397

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0936

Gnomad4 AMR

AF:

0.0461

Gnomad4 ASJ

AF:

0.0279

Gnomad4 EAS

AF:

0.0185

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.0959

Gnomad4 NFE

AF:

0.0554

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.0624

Hom.:

Bravo

AF:

0.0628

Asia WGS

AF:

0.0980

AC:

339

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

May 13, 2021

GeneDx

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

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.3

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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