rs138247851

Variant names:

• chr1-183023599-A-G
• rs138247851
• NM_002293.4:c.-118A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-183023599-A-G
• chr1-183023599-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002293.4(LAMC1):​c.-118A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 748,908 control chromosomes in the GnomAD database, including 494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (322 hom., cov: 30)
  • Exomes 𝑓: 0.016 (172 hom.)
• Consequence: LAMC1 NM_002293.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.31
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-183023599-A-G is Benign according to our data. Variant chr1-183023599-A-G is described in ClinVar as Benign. ClinVar VariationId is 1282385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002293.4. 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
	LAMC1	NM_002293.4	MANE Select	c.-118A>G		5_prime_UTR	Exon 1 of 28	NP_002284.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMC1	ENST00000258341.5	TSL:1 MANE Select	c.-118A>G		5_prime_UTR	Exon 1 of 28	ENSP00000258341.3	P11047
	LAMC1	ENST00000920737.1		c.-118A>G		5_prime_UTR	Exon 1 of 29	ENSP00000590796.1
	LAMC1	ENST00000920738.1		c.-118A>G		5_prime_UTR	Exon 1 of 28	ENSP00000590797.1

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6856 AN: 151710 Hom.: 308 Cov.: 30

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00195

Gnomad SAS AF: 0.0793

Gnomad FIN AF: 0.00342

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.0403

GnomAD4 exome AF: 0.0156 AC: 9290 AN: 597090 Hom.: 172 Cov.: 8 AF XY: 0.0157 AC XY: 4496 AN XY: 286388

African (AFR) AF: 0.116 AC: 1377 AN: 11826

American (AMR) AF: 0.0223 AC: 94 AN: 4212

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 87 AN: 6824

East Asian (EAS) AF: 0.00104 AC: 12 AN: 11516

South Asian (SAS) AF: 0.0747 AC: 781 AN: 10452

European-Finnish (FIN) AF: 0.00646 AC: 83 AN: 12840

Middle Eastern (MID) AF: 0.0383 AC: 62 AN: 1618

European-Non Finnish (NFE) AF: 0.0120 AC: 6198 AN: 514444

Other (OTH) AF: 0.0255 AC: 596 AN: 23358

GnomAD4 genome AF: 0.0455 AC: 6903 AN: 151818 Hom.: 322 Cov.: 30 AF XY: 0.0446 AC XY: 3308 AN XY: 74212

African (AFR) AF: 0.118 AC: 4912 AN: 41462

American (AMR) AF: 0.0332 AC: 506 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3466

East Asian (EAS) AF: 0.00196 AC: 10 AN: 5110

South Asian (SAS) AF: 0.0798 AC: 385 AN: 4826

European-Finnish (FIN) AF: 0.00342 AC: 36 AN: 10526

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0132 AC: 897 AN: 67864

Other (OTH) AF: 0.0399 AC: 84 AN: 2106

Alfa AF: 0.00905 Hom.: 7

Bravo AF: 0.0482

Asia WGS AF: 0.0500 AC: 174 AN: 3424

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.4
DANN	Benign	0.65
PhyloP100		-1.3
PromoterAI		-0.046	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs138247851; hg19: chr1-182992734;