19-49033197-A-G

Position:

• chr19-49033197-A-G

Variant summary

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

The NM_033378.2(CGB2):​c.468A>G​(p.Ser156Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 151,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 26)
  • Exomes 𝑓: 0.00047 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB2 NM_033378.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.183

Genes affected

CGB2 (HGNC:16722): (chorionic gonadotropin subunit beta 2) The beta subunit of chorionic gonadotropin (CGB) is encoded by six highly homologous and structurally similar genes that are arranged in tandem and inverted pairs on chromosome 19q13.3, and contiguous with the luteinizing hormone beta (LHB) subunit gene. The CGB genes are primarily distinguished by differences in the 5' untranscribed region. This gene was originally thought to be one of the two pseudogenes (CGB1 and CGB2) of CGB subunit, however, detection of CGB1 and CGB2 transcripts in vivo, and their presence on the polysomes, suggested that these transcripts are translated. To date, a protein product corresponding to CGB2 has not been isolated. The deduced sequence of the hypothetical protein of 132 aa does not share any similarity with that of functional CGB subunits (PMID:8954017). However, a 163 aa protein, translated from a different frame, is about the same size, and shares 98% identity with other CGB subunits. [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=-0.88).
• BP6: Variant 19-49033197-A-G is Benign according to our data. Variant chr19-49033197-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2650231.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.183 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB2	NM_033378.2	c.468A>G	p.Ser156Ser	synonymous_variant	3/3	ENST00000359342.7	NP_203696.2
CGB2	NM_001319065.2	c.432A>G	p.Ser144Ser	synonymous_variant	3/3		NP_001305994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGB2	ENST00000359342.7	c.468A>G	p.Ser156Ser	synonymous_variant	3/3	1	NM_033378.2	ENSP00000352295.6
ENSG00000267335	ENST00000591656.1	c.-28+3329T>C		intron_variant		2		ENSP00000466140.1
ENSG00000267335	ENST00000604577.1	c.9+3506T>C		intron_variant		1		ENSP00000474022.1
CGB2	ENST00000474913.1	c.*43A>G		downstream_gene_variant		1		ENSP00000471177.1

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 311 AN: 151042 Hom.: 1 Cov.: 26

Gnomad AFR AF: 0.00564

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000986

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000736

Gnomad OTH AF: 0.00242

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000471 AC: 687 AN: 1458976 Hom.: 3 Cov.: 35 AF XY: 0.000484 AC XY: 351 AN XY: 725844

Gnomad4 AFR exome AF: 0.00301

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000781

Gnomad4 SAS exome AF: 0.000592

Gnomad4 FIN exome AF: 0.000374

Gnomad4 NFE exome AF: 0.000361

Gnomad4 OTH exome AF: 0.000931

GnomAD4 genome AF: 0.00208 AC: 314 AN: 151156 Hom.: 1 Cov.: 26 AF XY: 0.00206 AC XY: 152 AN XY: 73898

Gnomad4 AFR AF: 0.00570

Gnomad4 AMR AF: 0.000984

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.000736

Gnomad4 OTH AF: 0.00239

Alfa AF: 0.00103 Hom.: 0

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

Sep 01, 2022

CGB2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.62

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: rs766526327; hg19: chr19-49536454;