rs2278544
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002299.4(LCT):āc.5568T>Cā(p.Ala1856=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 1,603,220 control chromosomes in the GnomAD database, including 442,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.60 ( 29596 hom., cov: 31)
Exomes š: 0.74 ( 413239 hom. )
Consequence
LCT
NM_002299.4 synonymous
NM_002299.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.140
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 2-135788540-A-G is Benign according to our data. Variant chr2-135788540-A-G is described in ClinVar as [Benign]. Clinvar id is 331164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135788540-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.14 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LCT | NM_002299.4 | c.5568T>C | p.Ala1856= | synonymous_variant | 17/17 | ENST00000264162.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LCT | ENST00000264162.7 | c.5568T>C | p.Ala1856= | synonymous_variant | 17/17 | 1 | NM_002299.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.597 AC: 90631AN: 151862Hom.: 29593 Cov.: 31
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GnomAD3 exomes AF: 0.621 AC: 156029AN: 251154Hom.: 52340 AF XY: 0.622 AC XY: 84402AN XY: 135746
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GnomAD4 exome AF: 0.739 AC: 1072495AN: 1451240Hom.: 413239 Cov.: 30 AF XY: 0.729 AC XY: 526552AN XY: 722514
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GnomAD4 genome ? AF: 0.597 AC: 90662AN: 151980Hom.: 29596 Cov.: 31 AF XY: 0.586 AC XY: 43523AN XY: 74260
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Lactose intolerance Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Congenital lactase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at