chr19-49048207-T-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_033183.3(CGB8):āc.181A>Gā(p.Met61Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000055 ( 0 hom., cov: 26)
Exomes š: 0.000042 ( 2 hom. )
Failed GnomAD Quality Control
Consequence
CGB8
NM_033183.3 missense, splice_region
NM_033183.3 missense, splice_region
Scores
8
9
Splicing: ADA: 0.009708
2
Clinical Significance
Conservation
PhyloP100: 1.01
Genes affected
CGB8 (HGNC:16453): (chorionic gonadotropin subunit beta 8) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 8 subunit of chorionic gonadotropin (CG). Glycoprotein hormones are heterodimers consisting of a common alpha subunit and an unique beta subunit which confers biological specificity. CG is produced by the trophoblastic cells of the placenta and stimulates the ovaries to synthesize the steroids that are essential for the maintenance of pregnancy. The beta subunit of CG is encoded by 6 genes which are arranged in tandem and inverted pairs on chromosome 19q13.3 and contiguous with the luteinizing hormone beta subunit gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.054333925).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CGB8 | NM_033183.3 | c.181A>G | p.Met61Val | missense_variant, splice_region_variant | 2/3 | ENST00000448456.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CGB8 | ENST00000448456.4 | c.181A>G | p.Met61Val | missense_variant, splice_region_variant | 2/3 | 1 | NM_033183.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 8AN: 145064Hom.: 0 Cov.: 26 FAILED QC
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000561 AC: 30AN: 53496Hom.: 1 AF XY: 0.000593 AC XY: 16AN XY: 26992
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000423 AC: 57AN: 1346062Hom.: 2 Cov.: 29 AF XY: 0.0000361 AC XY: 24AN XY: 664676
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000551 AC: 8AN: 145178Hom.: 0 Cov.: 26 AF XY: 0.0000707 AC XY: 5AN XY: 70718
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 03, 2022 | The c.181A>G (p.M61V) alteration is located in exon 2 (coding exon 2) of the CGB8 gene. This alteration results from a A to G substitution at nucleotide position 181, causing the methionine (M) at amino acid position 61 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
D
Sift4G
Benign
T
Vest4
MutPred
Gain of catalytic residue at M61 (P = 0.1041);
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at