NM_002291.3:c.*30A>C

Variant names:

• chr7-107923921-T-G
• rs7561
• NM_002291.3:c.*30A>C

Variant summary

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

The NM_002291.3(LAMB1):​c.*30A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,578,188 control chromosomes in the GnomAD database, including 284,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33597 hom., cov: 32)
  • Exomes 𝑓: 0.59 (250889 hom.)
• Consequence: LAMB1 NM_002291.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.44
• Publications: 20 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]

DLD (HGNC:2898): (dihydrolipoamide dehydrogenase) This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

DLD Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• pyruvate dehydrogenase E3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 7-107923921-T-G is Benign according to our data. Variant chr7-107923921-T-G is described in ClinVar as Benign. ClinVar VariationId is 1294643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 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.*30A>C		3_prime_UTR	Exon 34 of 34	NP_002282.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB1	ENST00000222399.11	TSL:1 MANE Select	c.*30A>C		3_prime_UTR	Exon 34 of 34	ENSP00000222399.6
	LAMB1	ENST00000943288.1		c.*30A>C		3_prime_UTR	Exon 34 of 34	ENSP00000613347.1
	LAMB1	ENST00000852248.1		c.*30A>C		3_prime_UTR	Exon 34 of 34	ENSP00000522307.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99774 AN: 151888 Hom.: 33543 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.634

GnomAD2 exomes AF: 0.608 AC: 134790 AN: 221624 AF XY: 0.603

Gnomad AFR exome AF: 0.783

Gnomad AMR exome AF: 0.571

Gnomad ASJ exome AF: 0.606

Gnomad EAS exome AF: 0.843

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.601

GnomAD4 exome AF: 0.589 AC: 839438 AN: 1426182 Hom.: 250889 Cov.: 30 AF XY: 0.587 AC XY: 416948 AN XY: 709734

African (AFR) AF: 0.796 AC: 24551 AN: 30848

American (AMR) AF: 0.586 AC: 20950 AN: 35734

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 14893 AN: 24662

East Asian (EAS) AF: 0.863 AC: 33262 AN: 38528

South Asian (SAS) AF: 0.549 AC: 44358 AN: 80728

European-Finnish (FIN) AF: 0.597 AC: 31461 AN: 52680

Middle Eastern (MID) AF: 0.573 AC: 3222 AN: 5624

European-Non Finnish (NFE) AF: 0.574 AC: 630939 AN: 1098562

Other (OTH) AF: 0.609 AC: 35802 AN: 58816

GnomAD4 genome AF: 0.657 AC: 99889 AN: 152006 Hom.: 33597 Cov.: 32 AF XY: 0.660 AC XY: 49057 AN XY: 74284

African (AFR) AF: 0.789 AC: 32734 AN: 41482

American (AMR) AF: 0.633 AC: 9659 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2083 AN: 3464

East Asian (EAS) AF: 0.850 AC: 4391 AN: 5166

South Asian (SAS) AF: 0.570 AC: 2749 AN: 4826

European-Finnish (FIN) AF: 0.613 AC: 6466 AN: 10554

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39624 AN: 67926

Other (OTH) AF: 0.636 AC: 1345 AN: 2114

Alfa AF: 0.605 Hom.: 11746

Bravo AF: 0.665

Asia WGS AF: 0.744 AC: 2584 AN: 3472

ClinVar

ClinVar submissions as Germline

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	-0.65
CADD	Benign	14
DANN	Benign	0.62
PhyloP100		1.4
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: rs7561; hg19: chr7-107564366; COSMIC: COSV52738058; COSMIC: COSV52738058;