7-107924094-G-A

Position:

chr7-107924094-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002291.3(LAMB1):c.5225-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,448,386 control chromosomes in the GnomAD database, including 209,408 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 31878 hom., cov: 31)

Exomes 𝑓: 0.54 ( 177530 hom. )

Consequence

LAMB1
NM_002291.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002593

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.308

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-107924094-G-A is Benign according to our data. Variant chr7-107924094-G-A is described in ClinVar as [Benign]. Clinvar id is 369575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107924094-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 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.5225-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000222399.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMB1	ENST00000222399.11 linkuse as main transcript	c.5225-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002291.3	P1

Frequencies

GnomAD3 genomes

AF:

0.646

AC:

97207

AN:

150368

Hom.:

31838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.701

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.845

Gnomad SAS

AF:

0.556

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.627

GnomAD3 exomes

AF:

0.564

AC:

95835

AN:

169878

Hom.:

25667

AF XY:

0.555

AC XY:

50609

AN XY:

91120

show subpopulations

Gnomad AFR exome

AF:

0.716

Gnomad AMR exome

AF:

0.524

Gnomad ASJ exome

AF:

0.568

Gnomad EAS exome

AF:

0.783

Gnomad SAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.550

Gnomad NFE exome

AF:

0.527

Gnomad OTH exome

AF:

0.561

GnomAD4 exome

AF:

0.541

AC:

701654

AN:

1297914

Hom.:

177530

Cov.:

AF XY:

0.539

AC XY:

346720

AN XY:

643238

show subpopulations

Gnomad4 AFR exome

AF:

0.714

Gnomad4 AMR exome

AF:

0.537

Gnomad4 ASJ exome

AF:

0.555

Gnomad4 EAS exome

AF:

0.796

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.529

Gnomad4 OTH exome

AF:

0.556

GnomAD4 genome

AF:

0.647

AC:

97301

AN:

150472

Hom.:

31878

Cov.:

AF XY:

0.649

AC XY:

47728

AN XY:

73488

show subpopulations

Gnomad4 AFR

AF:

0.767

Gnomad4 AMR

AF:

0.629

Gnomad4 ASJ

AF:

0.601

Gnomad4 EAS

AF:

0.844

Gnomad4 SAS

AF:

0.556

Gnomad4 FIN

AF:

0.606

Gnomad4 NFE

AF:

0.579

Gnomad4 OTH

AF:

0.629

Alfa

AF:

0.615

Hom.:

3529

Asia WGS

AF:

0.720

AC:

2490

AN:

3458

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 08, 2016

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. -

Pyruvate dehydrogenase complex deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Maple syrup urine disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Leigh syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cobblestone lissencephaly without muscular or ocular involvement

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.35

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0

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