Genetic Variant LAMA1:c.*416C>A (chr18-6941663-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005559.4(LAMA1):c.*416C>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 232,064 control chromosomes in the GnomAD database, including 24,291 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 15123 hom., cov: 32)

Exomes 𝑓: 0.46 ( 9168 hom. )

Consequence

LAMA1
NM_005559.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.00

Publications

8 publications found

Variant links:

Genes affected

LAMA1 (HGNC:6481): (laminin subunit alpha 1) This gene encodes one of the alpha 1 subunits of laminin. The laminins are a family of extracellular matrix glycoproteins that have a heterotrimeric structure consisting of an alpha, beta and gamma chain. These proteins make up a major component of the basement membrane and have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Mutations in this gene may be associated with Poretti-Boltshauser syndrome. [provided by RefSeq, Sep 2014]

LAMA1 Gene-Disease associations (from GenCC):

ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

LAMA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005559.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA1	NM_005559.4	MANE Select	c.*416C>A		downstream_gene	N/A	NP_005550.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LAMA1	ENST00000389658.4	TSL:1 MANE Select	c.*416C>A	downstream_gene	N/A	ENSP00000374309.3	P25391
LAMA1	ENST00000940203.1		c.*416C>A	downstream_gene	N/A	ENSP00000610262.1
LAMA1	ENST00000940200.1		c.*416C>A	downstream_gene	N/A	ENSP00000610259.1

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65530

AN:

151888

Hom.:

15118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.422

GnomAD4 exome

AF:

0.456

AC:

36512

AN:

80058

Hom.:

9168

AF XY:

0.440

AC XY:

18917

AN XY:

42970

show subpopulations

African (AFR)

AF:

0.341

AC:

633

AN:

1856

American (AMR)

AF:

0.276

AC:

1092

AN:

3956

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

904

AN:

1854

East Asian (EAS)

AF:

0.203

AC:

790

AN:

3898

South Asian (SAS)

AF:

0.280

AC:

3537

AN:

12642

European-Finnish (FIN)

AF:

0.554

AC:

2083

AN:

3758

Middle Eastern (MID)

AF:

0.426

AC:

110

AN:

258

European-Non Finnish (NFE)

AF:

0.532

AC:

25594

AN:

48102

Other (OTH)

AF:

0.474

AC:

1769

AN:

3734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

864

1728

2592

3456

4320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.431

AC:

65553

AN:

152006

Hom.:

15123

Cov.:

AF XY:

0.424

AC XY:

31481

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.332

AC:

13762

AN:

41460

American (AMR)

AF:

0.323

AC:

4928

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1685

AN:

3468

East Asian (EAS)

AF:

0.186

AC:

959

AN:

5164

South Asian (SAS)

AF:

0.285

AC:

1373

AN:

4814

European-Finnish (FIN)

AF:

0.550

AC:

5796

AN:

10542

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.524

AC:

35612

AN:

67970

Other (OTH)

AF:

0.422

AC:

892

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1800

3599

5399

7198

8998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.483

Hom.:

55840

Bravo

AF:

0.409

Asia WGS

AF:

0.258

AC:

899

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.0

(source)

DANN

Benign

0.56

PhyloP100

2.0

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over