chr8-64596702-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004820.5(CYP7B1):c.1461G>A(p.Leu487=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,420 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
CYP7B1
NM_004820.5 synonymous
NM_004820.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.809
Genes affected
CYP7B1 (HGNC:2652): (cytochrome P450 family 7 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway of extrahepatic tissues, which converts cholesterol to bile acids. This enzyme likely plays a minor role in total bile acid synthesis, but may also be involved in the development of atherosclerosis, neurosteroid metabolism and sex hormone synthesis. Mutations in this gene have been associated with hereditary spastic paraplegia (SPG5 or HSP), an autosomal recessive disorder. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 8-64596702-C-T is Benign according to our data. Variant chr8-64596702-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 759586.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.809 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP7B1 | NM_004820.5 | c.1461G>A | p.Leu487= | synonymous_variant | 6/6 | ENST00000310193.4 | |
CYP7B1 | XM_017014002.2 | c.1527G>A | p.Leu509= | synonymous_variant | 7/7 | ||
CYP7B1 | NM_001324112.2 | c.1234-6858G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP7B1 | ENST00000310193.4 | c.1461G>A | p.Leu487= | synonymous_variant | 6/6 | 1 | NM_004820.5 | P1 | |
CYP7B1 | ENST00000523954.1 | n.508-6858G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461238Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726906
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 11, 2023 | - - |
Computational scores
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Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at