chr2-135788089-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_002299.4(LCT):c.*235C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000993 in 559,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00097 ( 0 hom. )
Consequence
LCT
NM_002299.4 3_prime_UTR
NM_002299.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.01
Genes affected
LCT (HGNC:6530): (lactase) The protein encoded by this gene belongs to the glycosyl hydrolase 1 family of proteins. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme is integral to the plasma membrane and has both phlorizin hydrolase activity and lactase activity. Mutations in this gene are associated with congenital lactase deficiency. Polymorphisms in this gene are associated with lactase persistence, in which intestinal lactase activity persists at childhood levels into adulthood. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 2-135788089-G-A is Benign according to our data. Variant chr2-135788089-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 894024.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LCT | NM_002299.4 | c.*235C>T | 3_prime_UTR_variant | 17/17 | ENST00000264162.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LCT | ENST00000264162.7 | c.*235C>T | 3_prime_UTR_variant | 17/17 | 1 | NM_002299.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00106 AC: 162AN: 152156Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000966 AC: 393AN: 406902Hom.: 0 Cov.: 0 AF XY: 0.000921 AC XY: 200AN XY: 217138
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GnomAD4 genome AF: 0.00106 AC: 162AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.00114 AC XY: 85AN XY: 74450
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital lactase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at