X-153862727-G-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001278116.2(L1CAM):c.3710C>T(p.Ala1237Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,210,824 control chromosomes in the GnomAD database, including 1 homozygotes. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001278116.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
L1CAM | NM_001278116.2 | c.3710C>T | p.Ala1237Val | missense_variant | 29/29 | ENST00000370060.7 | NP_001265045.1 | |
L1CAM | NM_000425.5 | c.3710C>T | p.Ala1237Val | missense_variant | 28/28 | NP_000416.1 | ||
L1CAM | NM_024003.3 | c.3698C>T | p.Ala1233Val | missense_variant | 27/27 | NP_076493.1 | ||
L1CAM | NM_001143963.2 | c.3683C>T | p.Ala1228Val | missense_variant | 26/26 | NP_001137435.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000709 AC: 8AN: 112889Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 35045
GnomAD3 exomes AF: 0.0000770 AC: 14AN: 181770Hom.: 1 AF XY: 0.0000744 AC XY: 5AN XY: 67208
GnomAD4 exome AF: 0.0000301 AC: 33AN: 1097935Hom.: 1 Cov.: 30 AF XY: 0.0000275 AC XY: 10AN XY: 363323
GnomAD4 genome AF: 0.0000709 AC: 8AN: 112889Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 35045
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The L1CAM p.Ala1233Val variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs370546591) and in control databases in 15 of 203715 chromosomes (1 homozygous; 5 hemizygous) at a frequency of 0.00007363 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 8 of 7656 chromosomes (freq: 0.001045), South Asian in 2 of 19073 chromosomes (freq: 0.000105), African in 1 of 19098 chromosomes (freq: 0.000052) and European (non-Finnish) in 4 of 91041 chromosomes (freq: 0.000044), but was not observed in the Latino, East Asian, European (Finnish), or Other populations. The p.Ala1233 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | L1CAM: BP4, BS2 - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 07, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at