chr19-49047920-T-G

Variant names:

• chr19-49047920-T-G
• rs1414372486
• NM_033183.3:c.233A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_033183.3(CGB8):​c.233A>C​(p.Asn78Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB8 NM_033183.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.30
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.061267257).
• BP6: Variant 19-49047920-T-G is Benign according to our data. Variant chr19-49047920-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2381382.Status of the report is criteria_provided_single_submitter, 1 stars.

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.233A>C	p.Asn78Thr	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.233A>C	p.Asn78Thr	missense	Exon 3 of 3	ENSP00000403649.2	P0DN86-1
	CGB8	ENST00000933082.1		c.65A>C	p.Asn22Thr	missense	Exon 2 of 2	ENSP00000603141.1

Frequencies

GnomAD3 genomes AF: 0.000154 AC: 22 AN: 142456 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000210

Gnomad SAS AF: 0.00115

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000122

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 6 AN: 53804 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000191

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000993

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000191 AC: 207 AN: 1085694 Hom.: 0 Cov.: 14 AF XY: 0.000240 AC XY: 132 AN XY: 549230

African (AFR) AF: 0.000199 AC: 5 AN: 25098

American (AMR) AF: 0.000194 AC: 7 AN: 36158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20244

East Asian (EAS) AF: 0.00 AC: 0 AN: 37538

South Asian (SAS) AF: 0.000787 AC: 55 AN: 69910

European-Finnish (FIN) AF: 0.0000281 AC: 1 AN: 35620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3336

European-Non Finnish (NFE) AF: 0.000160 AC: 130 AN: 810186

Other (OTH) AF: 0.000189 AC: 9 AN: 47604

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000154 AC: 22 AN: 142564 Hom.: 0 Cov.: 24 AF XY: 0.000173 AC XY: 12 AN XY: 69272

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

African (AFR) AF: 0.000165 AC: 6 AN: 36428

American (AMR) AF: 0.000136 AC: 2 AN: 14662

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

East Asian (EAS) AF: 0.000210 AC: 1 AN: 4754

South Asian (SAS) AF: 0.00115 AC: 5 AN: 4358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.000122 AC: 8 AN: 65768

Other (OTH) AF: 0.00 AC: 0 AN: 1952

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000154435), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000123 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	5.4
DANN	Benign	0.65
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.77	T
PhyloP100		3.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	2.9	N
REVEL	Benign	0.22
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.13
MVP		0.40
MPC		0.0056
ClinPred		0.026	T
GERP RS		0.69
gMVP		0.021
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1414372486; hg19: chr19-49551177;