rs7788778

Variant names:

• chr7-107961078-T-C
• rs7788778
• NM_002291.3:c.2109+128A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002291.3(LAMB1):​c.2109+128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,000,462 control chromosomes in the GnomAD database, including 46,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5659 hom., cov: 32)
  • Exomes 𝑓: 0.31 (41331 hom.)
• Consequence: LAMB1 NM_002291.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.00
• Publications: 9 publications found

Genes affected

LAMB1 (HGNC:6486): (laminin subunit beta 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 are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form 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 beta chain isoform laminin, beta 1. The beta 1 chain has 7 structurally distinct domains which it shares with other beta chain isomers. The C-terminal helical region containing domains I and II are separated by domain alpha, domains III and V contain several EGF-like repeats, and domains IV and VI have a globular conformation. Laminin, beta 1 is expressed in most tissues that produce basement membranes, and is one of the 3 chains constituting laminin 1, the first laminin isolated from Engelbreth-Holm-Swarm (EHS) tumor. A sequence in the beta 1 chain that is involved in cell attachment, chemotaxis, and binding to the laminin receptor was identified and shown to have the capacity to inhibit metastasis. [provided by RefSeq, Aug 2011]

LAMB1 Gene-Disease associations (from GenCC):

• cobblestone lissencephaly without muscular or ocular involvement

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia, Genomics England PanelApp, G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-107961078-T-C is Benign according to our data. Variant chr7-107961078-T-C is described in ClinVar as Benign. ClinVar VariationId is 682976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002291.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB1	NM_002291.3	MANE Select	c.2109+128A>G		intron	N/A	NP_002282.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB1	ENST00000222399.11	TSL:1 MANE Select	c.2109+128A>G		intron	N/A	ENSP00000222399.6
	LAMB1	ENST00000393560.5	TSL:1	c.2109+128A>G		intron	N/A	ENSP00000377190.1
	LAMB1	ENST00000677793.1		c.2109+128A>G		intron	N/A	ENSP00000504020.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38406 AN: 151920 Hom.: 5661 Cov.: 32

Gnomad AFR AF: 0.0977

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.306 AC: 259736 AN: 848424 Hom.: 41331 AF XY: 0.307 AC XY: 132944 AN XY: 433624

African (AFR) AF: 0.0900 AC: 1829 AN: 20320

American (AMR) AF: 0.289 AC: 7208 AN: 24982

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 4698 AN: 16874

East Asian (EAS) AF: 0.255 AC: 8995 AN: 35300

South Asian (SAS) AF: 0.270 AC: 15273 AN: 56566

European-Finnish (FIN) AF: 0.351 AC: 14445 AN: 41144

Middle Eastern (MID) AF: 0.307 AC: 1020 AN: 3322

European-Non Finnish (NFE) AF: 0.319 AC: 194701 AN: 610534

Other (OTH) AF: 0.294 AC: 11567 AN: 39382

GnomAD4 genome AF: 0.253 AC: 38413 AN: 152038 Hom.: 5659 Cov.: 32 AF XY: 0.254 AC XY: 18838 AN XY: 74306

African (AFR) AF: 0.0977 AC: 4055 AN: 41504

American (AMR) AF: 0.253 AC: 3870 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1317 AN: 5154

South Asian (SAS) AF: 0.283 AC: 1361 AN: 4814

European-Finnish (FIN) AF: 0.355 AC: 3748 AN: 10568

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22040 AN: 67946

Other (OTH) AF: 0.259 AC: 545 AN: 2104

Alfa AF: 0.301 Hom.: 13713

Bravo AF: 0.239

Asia WGS AF: 0.247 AC: 856 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.087
DANN	Benign	0.46
PhyloP100		-2.0
Mutation Taster		=100/0	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: rs7788778; hg19: chr7-107601523;