chr19-49048207-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033183.3(CGB8):ā€‹c.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

Scores

8
9
Splicing: ADA: 0.009708
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01
Variant links:
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]

Genome browser will be placed here

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
CGB8NM_033183.3 linkuse as main transcriptc.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
CGB8ENST00000448456.4 linkuse as main transcriptc.181A>G p.Met61Val missense_variant, splice_region_variant 2/31 NM_033183.3 P1P0DN86-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
8
AN:
145064
Hom.:
0
Cov.:
26
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00161
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000561
AC:
30
AN:
53496
Hom.:
1
AF XY:
0.000593
AC XY:
16
AN XY:
26992
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00383
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000423
AC:
57
AN:
1346062
Hom.:
2
Cov.:
29
AF XY:
0.0000361
AC XY:
24
AN XY:
664676
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000275
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00138
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000884
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000533
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000551
AC:
8
AN:
145178
Hom.:
0
Cov.:
26
AF XY:
0.0000707
AC XY:
5
AN XY:
70718
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00161
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340

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 submitterclinical testingAmbry GeneticsFeb 03, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
23
DANN
Uncertain
0.98
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.074
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.90
D
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.054
T
MetaSVM
Uncertain
0.049
D
MutationTaster
Benign
1.0
D;N;N
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-1.8
N
REVEL
Uncertain
0.57
Sift
Benign
0.035
D
Sift4G
Benign
0.067
T
Vest4
0.16
MutPred
0.60
Gain of catalytic residue at M61 (P = 0.1041);
MVP
0.76
MPC
0.011
ClinPred
0.076
T
GERP RS
1.8
gMVP
0.062

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0097
dbscSNV1_RF
Benign
0.11
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1463964361; hg19: chr19-49551464; API