1-209618584-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000228.3(LAMB3):c.2777C>A(p.Ala926Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,614,230 control chromosomes in the GnomAD database, including 2,972 homozygotes. In-silico tool predicts 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. A926G) has been classified as Benign.
Frequency
Consequence
NM_000228.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMB3 | NM_000228.3 | c.2777C>A | p.Ala926Asp | missense_variant | Exon 19 of 23 | ENST00000356082.9 | NP_000219.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMB3 | ENST00000356082.9 | c.2777C>A | p.Ala926Asp | missense_variant | Exon 19 of 23 | 1 | NM_000228.3 | ENSP00000348384.3 | ||
LAMB3 | ENST00000367030.7 | c.2777C>A | p.Ala926Asp | missense_variant | Exon 19 of 23 | 1 | ENSP00000355997.3 | |||
LAMB3 | ENST00000391911.5 | c.2777C>A | p.Ala926Asp | missense_variant | Exon 18 of 22 | 1 | ENSP00000375778.1 | |||
LAMB3 | ENST00000455193.1 | c.-17C>A | 5_prime_UTR_variant | Exon 1 of 4 | 2 | ENSP00000398683.1 |
Frequencies
GnomAD3 genomes AF: 0.0325 AC: 4954AN: 152238Hom.: 293 Cov.: 34
GnomAD3 exomes AF: 0.0593 AC: 14906AN: 251360Hom.: 1119 AF XY: 0.0591 AC XY: 8035AN XY: 135876
GnomAD4 exome AF: 0.0378 AC: 55262AN: 1461874Hom.: 2678 Cov.: 34 AF XY: 0.0394 AC XY: 28683AN XY: 727240
GnomAD4 genome AF: 0.0325 AC: 4949AN: 152356Hom.: 294 Cov.: 34 AF XY: 0.0341 AC XY: 2541AN XY: 74512
ClinVar
Submissions by phenotype
not specified Benign:2
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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. -
not provided Benign:2
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Junctional epidermolysis bullosa, non-Herlitz type Benign:1
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Amelogenesis imperfecta type 1A Benign:1
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Junctional epidermolysis bullosa gravis of Herlitz Benign:1
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Junctional epidermolysis bullosa Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at