19-49023006-G-A

Position:

• chr19-49023006-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000737.5(CGB3):​c.378C>T​(p.His126His) variant causes a synonymous 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 17)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB3 NM_000737.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.02

Genes affected

CGB3 (HGNC:1886): (chorionic gonadotropin subunit beta 3) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 3 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]

ENSG00000267335 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-49023006-G-A is Benign according to our data. Variant chr19-49023006-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.02 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB3	NM_000737.5	c.378C>T	p.His126His	synonymous_variant	3/3	ENST00000357383.4	NP_000728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGB3	ENST00000357383.4	c.378C>T	p.His126His	synonymous_variant	3/3	1	NM_000737.5	ENSP00000349954.2
ENSG00000267335	ENST00000591656.1	c.336C>T	p.His112His	synonymous_variant	3/3	2		ENSP00000466140.1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000431 AC: 6 AN: 1390756 Hom.: 0 Cov.: 33 AF XY: 0.00000435 AC XY: 3 AN XY: 689930

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000603

Gnomad4 ASJ exome AF: 0.0000430

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000186

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 17

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

CGB3: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.10
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs2039635415; hg19: chr19-49526263;