7-107953544-T-C

Variant names:

• chr7-107953544-T-C
• rs20556
• NM_002291.3:c.3065A>G
• LAMB1 p.Gln1022Arg

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.3065A>G​(p.Gln1022Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,612,288 control chromosomes in the GnomAD database, including 329,260 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1022L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.66 (33752 hom., cov: 32)
  • Exomes 𝑓: 0.63 (295508 hom.)
• Consequence: LAMB1 NM_002291.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.13
• Publications: 42 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, Unknown Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=7.994713E-7).
• BP6: Variant 7-107953544-T-C is Benign according to our data. Variant chr7-107953544-T-C is described in ClinVar as Benign. ClinVar VariationId is 380837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB1	NM_002291.3	MANE Select	c.3065A>G	p.Gln1022Arg	missense	Exon 22 of 34	NP_002282.2	P07942

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB1	ENST00000222399.11	TSL:1 MANE Select	c.3065A>G	p.Gln1022Arg	missense	Exon 22 of 34	ENSP00000222399.6	P07942
	LAMB1	ENST00000943288.1		c.3065A>G	p.Gln1022Arg	missense	Exon 22 of 34	ENSP00000613347.1
	LAMB1	ENST00000852248.1		c.3065A>G	p.Gln1022Arg	missense	Exon 22 of 34	ENSP00000522307.1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 100994 AN: 151960 Hom.: 33715 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.642

GnomAD2 exomes AF: 0.647 AC: 162392 AN: 251096 AF XY: 0.641

Gnomad AFR exome AF: 0.704

Gnomad AMR exome AF: 0.625

Gnomad ASJ exome AF: 0.668

Gnomad EAS exome AF: 0.832

Gnomad FIN exome AF: 0.667

Gnomad NFE exome AF: 0.623

Gnomad OTH exome AF: 0.630

GnomAD4 exome AF: 0.634 AC: 925847 AN: 1460210 Hom.: 295508 Cov.: 37 AF XY: 0.632 AC XY: 459444 AN XY: 726488

African (AFR) AF: 0.710 AC: 23720 AN: 33432

American (AMR) AF: 0.632 AC: 28260 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 17467 AN: 26128

East Asian (EAS) AF: 0.855 AC: 33914 AN: 39674

South Asian (SAS) AF: 0.595 AC: 51323 AN: 86202

European-Finnish (FIN) AF: 0.663 AC: 35388 AN: 53414

Middle Eastern (MID) AF: 0.560 AC: 3223 AN: 5754

European-Non Finnish (NFE) AF: 0.625 AC: 693854 AN: 1110554

Other (OTH) AF: 0.641 AC: 38698 AN: 60336

GnomAD4 genome AF: 0.665 AC: 101087 AN: 152078 Hom.: 33752 Cov.: 32 AF XY: 0.667 AC XY: 49608 AN XY: 74320

African (AFR) AF: 0.709 AC: 29393 AN: 41478

American (AMR) AF: 0.655 AC: 10005 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2379 AN: 3470

East Asian (EAS) AF: 0.842 AC: 4359 AN: 5176

South Asian (SAS) AF: 0.612 AC: 2952 AN: 4824

European-Finnish (FIN) AF: 0.681 AC: 7196 AN: 10562

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42695 AN: 67972

Other (OTH) AF: 0.644 AC: 1357 AN: 2108

Alfa AF: 0.641 Hom.: 117846

Bravo AF: 0.662

Asia WGS AF: 0.743 AC: 2582 AN: 3478

EpiCase AF: 0.618

EpiControl AF: 0.623

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.075
DANN	Benign	0.29
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	8.0e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.11	N
PhyloP100		-1.1
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.091
Sift	Benign	1.0	T
Sift4G	Benign	0.67	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.074
gMVP		0.39
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs20556;

hg19: chr7-107593989;

COSMIC: COSV55965478;

COSMIC: COSV55965478;