Variant 7-107923921-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.44

Variant links:

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 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 id is 1294643.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMB1	NM_002291.3 linkuse as main transcript	c.*30A>C		3_prime_UTR_variant	34/34	ENST00000222399.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMB1	ENST00000222399.11 linkuse as main transcript	c.*30A>C		3_prime_UTR_variant	34/34	1	NM_002291.3	P1

Frequencies

GnomAD3 genomes

AF:

0.657

AC:

99774

AN:

151888

Hom.:

33543

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.608

AC:

134790

AN:

221624

Hom.:

41907

AF XY:

0.603

AC XY:

72598

AN XY:

120494

show subpopulations

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 SAS exome

AF:

0.552

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.:

AF XY:

0.587

AC XY:

416948

AN XY:

709734

show subpopulations

Gnomad4 AFR exome

AF:

0.796

Gnomad4 AMR exome

AF:

0.586

Gnomad4 ASJ exome

AF:

0.604

Gnomad4 EAS exome

AF:

0.863

Gnomad4 SAS exome

AF:

0.549

Gnomad4 FIN exome

AF:

0.597

Gnomad4 NFE exome

AF:

0.574

Gnomad4 OTH exome

AF:

0.609

GnomAD4 genome

AF:

0.657

AC:

99889

AN:

152006

Hom.:

33597

Cov.:

AF XY:

0.660

AC XY:

49057

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.789

Gnomad4 AMR

AF:

0.633

Gnomad4 ASJ

AF:

0.601

Gnomad4 EAS

AF:

0.850

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.613

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.636

Alfa

AF:

0.602

Hom.:

9496

Bravo

AF:

0.665

Asia WGS

AF:

0.744

AC:

2584

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over