NM_033183.3:c.77G>A

Variant names:

• chr19-49048311-C-T
• rs1252727580
• NM_033183.3:c.77G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033183.3(CGB8):​c.77G>A​(p.Arg26Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (1 hom., cov: 26)
  • Exomes 𝑓: 0.00050 (8 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB8 NM_033183.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017039448).

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.77G>A	p.Arg26Gln	missense	Exon 2 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.77G>A	p.Arg26Gln	missense	Exon 2 of 3	ENSP00000403649.2	P0DN86-1
	CGB8	ENST00000933082.1		c.16-342G>A		intron	N/A	ENSP00000603141.1

Frequencies

GnomAD3 genomes AF: 0.000288 AC: 43 AN: 149212 Hom.: 1 Cov.: 26

Gnomad AFR AF: 0.0000256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00886

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000828 AC: 45 AN: 54332 AF XY: 0.000987

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: 0.00

Gnomad OTH exome AF: 0.000524

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000503 AC: 725 AN: 1441834 Hom.: 8 Cov.: 32 AF XY: 0.000734 AC XY: 527 AN XY: 717620

African (AFR) AF: 0.00 AC: 0 AN: 32736

American (AMR) AF: 0.00 AC: 0 AN: 44382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39612

South Asian (SAS) AF: 0.00792 AC: 680 AN: 85900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38440

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4118

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1110654

Other (OTH) AF: 0.000517 AC: 31 AN: 59956

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000288 AC: 43 AN: 149328 Hom.: 1 Cov.: 26 AF XY: 0.000494 AC XY: 36 AN XY: 72858

African (AFR) AF: 0.0000255 AC: 1 AN: 39216

American (AMR) AF: 0.00 AC: 0 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5066

South Asian (SAS) AF: 0.00887 AC: 42 AN: 4736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67788

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000642

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	-0.37	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	1.0
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.32	T
PhyloP100		1.6
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.30
Sift	Benign	0.14	T
Sift4G	Benign	0.22	T
Vest4		0.36
MutPred		0.59		Gain of helix (P = 0.0425)
MVP		0.40
MPC		0.0076
ClinPred		0.047	T
GERP RS		1.8
gMVP		0.079
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: rs1252727580; hg19: chr19-49551568;