rs12961939

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005559.4(LAMA1):c.4729T>G(p.Ser1577Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,613,506 control chromosomes in the GnomAD database, including 49,325 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3828 hom., cov: 33)

Exomes 𝑓: 0.24 ( 45497 hom. )

Consequence

LAMA1
NM_005559.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.43

Publications

28 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, G2P, Labcorp Genetics (formerly Invitae)

LAMA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009468079).

BP6

Variant 18-6997819-A-C is Benign according to our data. Variant chr18-6997819-A-C is described in ClinVar as Benign. ClinVar VariationId is 803471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 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.4729T>G	p.Ser1577Ala	missense	Exon 33 of 63	NP_005550.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAMA1	ENST00000389658.4	TSL:1 MANE Select	c.4729T>G	p.Ser1577Ala	missense	Exon 33 of 63	ENSP00000374309.3	P25391
LAMA1	ENST00000940203.1		c.4822T>G	p.Ser1608Ala	missense	Exon 34 of 64	ENSP00000610262.1
LAMA1	ENST00000940200.1		c.4729T>G	p.Ser1577Ala	missense	Exon 33 of 63	ENSP00000610259.1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32638

AN:

152114

Hom.:

3824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.0575

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.228

GnomAD2 exomes

AF:

0.204

AC:

51254

AN:

251450

AF XY:

0.205

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.318

Gnomad EAS exome

AF:

0.0511

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.242

AC:

353748

AN:

1461274

Hom.:

45497

Cov.:

AF XY:

0.238

AC XY:

173324

AN XY:

726960

show subpopulations

African (AFR)

AF:

0.158

AC:

5276

AN:

33462

American (AMR)

AF:

0.139

AC:

6229

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

8335

AN:

26132

East Asian (EAS)

AF:

0.0585

AC:

2323

AN:

39696

South Asian (SAS)

AF:

0.102

AC:

8793

AN:

86254

European-Finnish (FIN)

AF:

0.260

AC:

13880

AN:

53390

Middle Eastern (MID)

AF:

0.264

AC:

1525

AN:

5766

European-Non Finnish (NFE)

AF:

0.264

AC:

293265

AN:

1111470

Other (OTH)

AF:

0.234

AC:

14122

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

14314

28628

42943

57257

71571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9708

19416

29124

38832

48540

<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:

0.215

AC:

32658

AN:

152232

Hom.:

3828

Cov.:

AF XY:

0.210

AC XY:

15607

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.155

AC:

6438

AN:

41532

American (AMR)

AF:

0.194

AC:

2964

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1146

AN:

3470

East Asian (EAS)

AF:

0.0573

AC:

297

AN:

5186

South Asian (SAS)

AF:

0.0997

AC:

481

AN:

4824

European-Finnish (FIN)

AF:

0.258

AC:

2730

AN:

10594

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17826

AN:

68022

Other (OTH)

AF:

0.228

AC:

482

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1321

2642

3964

5285

6606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.246

Hom.:

22309

Bravo

AF:

0.209

TwinsUK

AF:

0.273

AC:

1011

ALSPAC

AF:

0.265

AC:

1020

ESP6500AA

AF:

0.149

AC:

658

ESP6500EA

AF:

0.269

AC:

2311

ExAC

AF:

0.203

AC:

24583

Asia WGS

AF:

0.105

AC:

362

AN:

3478

EpiCase

AF:

0.274

EpiControl

AF:

0.273

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.095

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0095

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.5

PhyloP100

3.4

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.3

REVEL

Benign

0.15

Sift

Uncertain

0.019

Sift4G

Benign

0.14

Polyphen

0.36

Vest4

0.14

MPC

0.16

ClinPred

0.040

GERP RS

4.2

Varity_R

0.11

gMVP

0.40

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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