1-183124740-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002293.4(LAMC1):c.2511T>C(p.Asn837Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,613,798 control chromosomes in the GnomAD database, including 262,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21118 hom., cov: 32)

Exomes 𝑓: 0.57 ( 241153 hom. )

Consequence

LAMC1
NM_002293.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.74

Publications

26 publications found

Variant links:

Genes affected

LAMC1 (HGNC:6492): (laminin subunit gamma 1) 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, composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively), have 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. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the gamma chain isoform laminin, gamma 1. The gamma 1 chain, formerly thought to be a beta chain, contains structural domains similar to beta chains, however, lacks the short alpha region separating domains I and II. The structural organization of this gene also suggested that it had diverged considerably from the beta chain genes. Embryos of transgenic mice in which both alleles of the gamma 1 chain gene were inactivated by homologous recombination, lacked basement membranes, indicating that laminin, gamma 1 chain is necessary for laminin heterotrimer assembly. It has been inferred by analogy with the strikingly similar 3' UTR sequence in mouse laminin gamma 1 cDNA, that multiple polyadenylation sites are utilized in human to generate the 2 different sized mRNAs (5.5 and 7.5 kb) seen on Northern analysis. [provided by RefSeq, Aug 2011]

LAMC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-183124740-T-C is Benign according to our data. Variant chr1-183124740-T-C is described in ClinVar as [Benign]. Clinvar id is 1296709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMC1	NM_002293.4 link	c.2511T>C	p.Asn837Asn	synonymous_variant	Exon 14 of 28	ENST00000258341.5	NP_002284.3	P11047Q6NVY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMC1	ENST00000258341.5 link	c.2511T>C	p.Asn837Asn	synonymous_variant	Exon 14 of 28	1	NM_002293.4	ENSP00000258341.3		P11047

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78694

AN:

151952

Hom.:

21064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.373

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.498

Gnomad EAS

AF:

0.611

Gnomad SAS

AF:

0.648

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.543

GnomAD2 exomes

AF:

0.580

AC:

145878

AN:

251346

AF XY:

0.583

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.680

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.621

Gnomad FIN exome

AF:

0.596

Gnomad NFE exome

AF:

0.559

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.571

AC:

835260

AN:

1461726

Hom.:

241153

Cov.:

AF XY:

0.574

AC XY:

417515

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.362

AC:

12114

AN:

33480

American (AMR)

AF:

0.676

AC:

30224

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

12884

AN:

26136

East Asian (EAS)

AF:

0.617

AC:

24507

AN:

39698

South Asian (SAS)

AF:

0.653

AC:

56309

AN:

86254

European-Finnish (FIN)

AF:

0.593

AC:

31659

AN:

53416

Middle Eastern (MID)

AF:

0.541

AC:

3119

AN:

5768

European-Non Finnish (NFE)

AF:

0.567

AC:

629990

AN:

1111866

Other (OTH)

AF:

0.571

AC:

34454

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

21173

42346

63519

84692

105865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17628

35256

52884

70512

88140

<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:

0.518

AC:

78800

AN:

152072

Hom.:

21118

Cov.:

AF XY:

0.525

AC XY:

38990

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.374

AC:

15525

AN:

41480

American (AMR)

AF:

0.619

AC:

9459

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

1729

AN:

3470

East Asian (EAS)

AF:

0.611

AC:

3162

AN:

5176

South Asian (SAS)

AF:

0.651

AC:

3136

AN:

4820

European-Finnish (FIN)

AF:

0.603

AC:

6375

AN:

10568

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.553

AC:

37589

AN:

67956

Other (OTH)

AF:

0.549

AC:

1158

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1908

3816

5725

7633

9541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.543

Hom.:

24454

Bravo

AF:

0.511

Asia WGS

AF:

0.643

AC:

2235

AN:

3478

EpiCase

AF:

0.564

EpiControl

AF:

0.560

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

- -

Oct 04, 2018

GeneDx

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

-0.84

CADD

Benign

0.14

(source)

DANN

Benign

0.31

PhyloP100

-1.7

Mutation Taster

=100/0

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

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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