rs2076222

Positions:

• chr1-209618584-G-C
• chr1-209618584-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000228.3(LAMB3):​c.2777C>G​(p.Ala926Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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. A926D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: LAMB3 NM_000228.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.32

Genes affected

LAMB3 (HGNC:6490): (laminin subunit beta 3) The product encoded by this gene is a laminin that belongs to a family of basement membrane proteins. This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, forms laminin-5. Mutations in this gene cause epidermolysis bullosa junctional Herlitz type, and generalized atrophic benign epidermolysis bullosa, diseases that are characterized by blistering of the skin. Multiple alternatively spliced transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-209618584-G-C is Benign according to our data. Variant chr1-209618584-G-C is described in ClinVar as [Benign]. Clinvar id is 1291217.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMB3	NM_000228.3	c.2777C>G	p.Ala926Gly	missense_variant	19/23	ENST00000356082.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMB3	ENST00000356082.9	c.2777C>G	p.Ala926Gly	missense_variant	19/23	1	NM_000228.3	P1
LAMB3	ENST00000367030.7	c.2777C>G	p.Ala926Gly	missense_variant	19/23	1		P1
LAMB3	ENST00000391911.5	c.2777C>G	p.Ala926Gly	missense_variant	18/22	1		P1
LAMB3	ENST00000455193.1	c.-17C>G		5_prime_UTR_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	.;T;.
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.6	M;M;M
MutationTaster	Benign	0.25	P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.014	D;D;D
Sift4G	Uncertain	0.023	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.39
MutPred		0.57		Gain of catalytic residue at A926 (P = 0.0169);Gain of catalytic residue at A926 (P = 0.0169);Gain of catalytic residue at A926 (P = 0.0169);
MVP		0.68
MPC		0.14
ClinPred		0.71	D
GERP RS		4.1
Varity_R		0.13
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-209791929;