18-7034509-T-G

Variant names:

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.2021A>C(p.Asn674Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,588 control chromosomes in the GnomAD database, including 38,064 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. N674N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.20 ( 3236 hom., cov: 33)

Exomes 𝑓: 0.21 ( 34828 hom. )

Consequence

LAMA1
NM_005559.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.538

Publications

27 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=0.002455771).

BP6

Variant 18-7034509-T-G is Benign according to our data. Variant chr18-7034509-T-G is described in ClinVar as Benign. ClinVar VariationId is 803473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA1	NM_005559.4 link	c.2021A>C	p.Asn674Thr	missense_variant	Exon 14 of 63	ENST00000389658.4	NP_005550.2	P25391

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4 link	c.2021A>C	p.Asn674Thr	missense_variant	Exon 14 of 63	1	NM_005559.4	ENSP00000374309.3		P25391
LAMA1	ENST00000579014.5 link	n.3036A>C		non_coding_transcript_exon_variant	Exon 13 of 62	2

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30412

AN:

152002

Hom.:

3228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.225

GnomAD2 exomes

AF:

0.197

AC:

49418

AN:

251384

AF XY:

0.198

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.237

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.214

AC:

313395

AN:

1461468

Hom.:

34828

Cov.:

AF XY:

0.213

AC XY:

155145

AN XY:

727072

show subpopulations

African (AFR)

AF:

0.166

AC:

5568

AN:

33478

American (AMR)

AF:

0.163

AC:

7285

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

7840

AN:

26132

East Asian (EAS)

AF:

0.121

AC:

4815

AN:

39694

South Asian (SAS)

AF:

0.135

AC:

11633

AN:

86250

European-Finnish (FIN)

AF:

0.234

AC:

12477

AN:

53412

Middle Eastern (MID)

AF:

0.307

AC:

1770

AN:

5768

European-Non Finnish (NFE)

AF:

0.224

AC:

249035

AN:

1111630

Other (OTH)

AF:

0.215

AC:

12972

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

12508

25016

37525

50033

62541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8440

16880

25320

33760

42200

<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:

0.200

AC:

30438

AN:

152120

Hom.:

3236

Cov.:

AF XY:

0.199

AC XY:

14763

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.161

AC:

6691

AN:

41526

American (AMR)

AF:

0.179

AC:

2739

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1046

AN:

3470

East Asian (EAS)

AF:

0.123

AC:

634

AN:

5158

South Asian (SAS)

AF:

0.129

AC:

624

AN:

4822

European-Finnish (FIN)

AF:

0.234

AC:

2477

AN:

10580

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.229

AC:

15550

AN:

67994

Other (OTH)

AF:

0.226

AC:

476

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1236

2472

3709

4945

6181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.220

Hom.:

18525

Bravo

AF:

0.197

TwinsUK

AF:

0.226

AC:

837

ALSPAC

AF:

0.228

AC:

880

ESP6500AA

AF:

0.164

AC:

724

ESP6500EA

AF:

0.231

AC:

1987

ExAC

AF:

0.193

AC:

23404

Asia WGS

AF:

0.115

AC:

399

AN:

3476

EpiCase

AF:

0.237

EpiControl

AF:

0.233

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 13, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome

Benign:2

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.014

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.057

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

PhyloP100

0.54

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.75

Vest4

0.10

MPC

0.12

ClinPred

0.028

GERP RS

4.8

Varity_R

0.072

gMVP

0.45

Mutation Taster

=85/15

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over