19-49047869-C-T

Variant names:

• chr19-49047869-C-T
• rs1273130331
• NM_033183.3:c.284G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_033183.3(CGB8):​c.284G>A​(p.Gly95Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB8 NM_033183.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033183.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB8	NM_033183.3	MANE Select	c.284G>A	p.Gly95Asp	missense	Exon 3 of 3	NP_149439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB8	ENST00000448456.4	TSL:1 MANE Select	c.284G>A	p.Gly95Asp	missense	Exon 3 of 3	ENSP00000403649.2	P0DN86-1
	CGB8	ENST00000933082.1		c.116G>A	p.Gly39Asp	missense	Exon 2 of 2	ENSP00000603141.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 16 AN: 143030 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000183

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000931 AC: 5 AN: 53684 AF XY: 0.000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000249

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000159 AC: 109 AN: 687558 Hom.: 0 Cov.: 9 AF XY: 0.000143 AC XY: 51 AN XY: 356186

African (AFR) AF: 0.00 AC: 0 AN: 19154

American (AMR) AF: 0.0000321 AC: 1 AN: 31144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17602

East Asian (EAS) AF: 0.00 AC: 0 AN: 32874

South Asian (SAS) AF: 0.00 AC: 0 AN: 57536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2610

European-Non Finnish (NFE) AF: 0.000224 AC: 103 AN: 460230

Other (OTH) AF: 0.000144 AC: 5 AN: 34644

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000112 AC: 16 AN: 143030 Hom.: 0 Cov.: 23 AF XY: 0.000101 AC XY: 7 AN XY: 69234

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000108 AC: 4 AN: 37186

American (AMR) AF: 0.00 AC: 0 AN: 14648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3368

East Asian (EAS) AF: 0.00 AC: 0 AN: 4756

South Asian (SAS) AF: 0.00 AC: 0 AN: 4330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.000183 AC: 12 AN: 65458

Other (OTH) AF: 0.00 AC: 0 AN: 1904

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000201987), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000184 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	0.0036
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	0.66	D
PhyloP100		2.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.013	D
Sift4G	Benign	0.20	T
Vest4		0.37
MutPred		0.71		Gain of solvent accessibility (P = 0.0354)
MVP		0.77
MPC		0.018
ClinPred		0.71	D
GERP RS		1.8
gMVP		0.027
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1273130331; hg19: chr19-49551126;