19-49047914-C-T

Variant names:

• chr19-49047914-C-T
• rs927750169
• NM_033183.3:c.239G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033183.3(CGB8):​c.239G>A​(p.Arg80His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB8 NM_033183.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.12
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11934757).

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.239G>A	p.Arg80His	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.239G>A	p.Arg80His	missense	Exon 3 of 3	ENSP00000403649.2	P0DN86-1
	CGB8	ENST00000933082.1		c.71G>A	p.Arg24His	missense	Exon 2 of 2	ENSP00000603141.1

Frequencies

GnomAD3 genomes AF: 0.000169 AC: 24 AN: 142418 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000661

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000372 AC: 2 AN: 53732 AF XY: 0.00

Gnomad AFR exome AF: 0.000384

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000236 AC: 22 AN: 933054 Hom.: 0 Cov.: 12 AF XY: 0.0000251 AC XY: 12 AN XY: 477296

African (AFR) AF: 0.000434 AC: 10 AN: 23034

American (AMR) AF: 0.0000580 AC: 2 AN: 34506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18970

East Asian (EAS) AF: 0.00 AC: 0 AN: 36640

South Asian (SAS) AF: 0.0000304 AC: 2 AN: 65742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3052

European-Non Finnish (NFE) AF: 0.0000104 AC: 7 AN: 673414

Other (OTH) AF: 0.0000234 AC: 1 AN: 42734

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000175 AC: 25 AN: 142520 Hom.: 0 Cov.: 24 AF XY: 0.000173 AC XY: 12 AN XY: 69210

African (AFR) AF: 0.000686 AC: 25 AN: 36432

American (AMR) AF: 0.00 AC: 0 AN: 14650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3366

East Asian (EAS) AF: 0.00 AC: 0 AN: 4752

South Asian (SAS) AF: 0.00 AC: 0 AN: 4396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65708

Other (OTH) AF: 0.00 AC: 0 AN: 1960

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000166

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	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	5.4
DANN	Benign	0.97
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.43	T
PhyloP100		-1.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.25
Sift	Benign	0.25	T
Sift4G	Benign	0.32	T
Vest4		0.086
MutPred		0.61		Gain of methylation at R83 (P = 0.0691)
MVP		0.49
MPC		0.0048
ClinPred		0.036	T
GERP RS		-1.9
gMVP		0.037
Mutation Taster		=100/0	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: rs927750169; hg19: chr19-49551171;