19-49047872-C-T

Variant names:

• chr19-49047872-C-T
• rs1259097854
• NM_033183.3:c.281G>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.281G>A​(p.Arg94His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB8 NM_033183.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12976548).

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.281G>A	p.Arg94His	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.281G>A	p.Arg94His	missense	Exon 3 of 3	ENSP00000403649.2	P0DN86-1
	CGB8	ENST00000933082.1		c.113G>A	p.Arg38His	missense	Exon 2 of 2	ENSP00000603141.1

Frequencies

GnomAD3 genomes AF: 0.0000140 AC: 2 AN: 142634 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000685

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: 0.0000932 AC: 5 AN: 53664 AF XY: 0.000111

Gnomad AFR exome AF: 0.000192

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000382

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000498

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000115 AC: 8 AN: 697556 Hom.: 0 Cov.: 9 AF XY: 0.0000111 AC XY: 4 AN XY: 361286

African (AFR) AF: 0.0000517 AC: 1 AN: 19352

American (AMR) AF: 0.00 AC: 0 AN: 31260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17692

East Asian (EAS) AF: 0.0000908 AC: 3 AN: 33022

South Asian (SAS) AF: 0.00 AC: 0 AN: 58010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2648

European-Non Finnish (NFE) AF: 0.00000853 AC: 4 AN: 468706

Other (OTH) AF: 0.00 AC: 0 AN: 34964

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000140 AC: 2 AN: 142634 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 69020

African (AFR) AF: 0.0000270 AC: 1 AN: 37020

American (AMR) AF: 0.0000685 AC: 1 AN: 14590

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4722

South Asian (SAS) AF: 0.00 AC: 0 AN: 4334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65362

Other (OTH) AF: 0.00 AC: 0 AN: 1886

Alfa AF: 0.00 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	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Uncertain	0.98
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.33	T
PhyloP100		2.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.040	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.17	T
Vest4		0.094
MutPred		0.47		Loss of methylation at R94 (P = 0.0271)
MVP		0.43
MPC		0.017
ClinPred		0.27	T
GERP RS		-0.67
gMVP		0.034
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: rs1259097854; hg19: chr19-49551129;