rs2303050

Positions:

• chr19-49032689-G-A
• chr19-49032689-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033378.2(CGB2):​c.177+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00097 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0015 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB2 NM_033378.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB2	NM_033378.2	c.177+18G>A		intron_variant		ENST00000359342.7	NP_203696.2
CGB2	NM_001319065.2	c.141+18G>A		intron_variant			NP_001305994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGB2	ENST00000359342.7	c.177+18G>A		intron_variant		1	NM_033378.2	ENSP00000352295.6
CGB2	ENST00000474913.1	c.141+18G>A		intron_variant		1		ENSP00000471177.1
ENSG00000267335	ENST00000591656.1	c.-28+3837C>T		intron_variant		2		ENSP00000466140.1
ENSG00000267335	ENST00000604577.1	c.9+4014C>T		intron_variant		1		ENSP00000474022.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 120 AN: 124122 Hom.: 0 Cov.: 16 FAILED QC

Gnomad AFR AF: 0.00108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000580

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00209

Gnomad SAS AF: 0.00122

Gnomad FIN AF: 0.000877

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000998

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00175 AC: 141 AN: 80802 Hom.: 0 AF XY: 0.00180 AC XY: 75 AN XY: 41706

Gnomad AFR exome AF: 0.00176

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00329

Gnomad SAS exome AF: 0.00196

Gnomad FIN exome AF: 0.00118

Gnomad NFE exome AF: 0.00162

Gnomad OTH exome AF: 0.00154

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00155 AC: 1512 AN: 975796 Hom.: 2 Cov.: 15 AF XY: 0.00149 AC XY: 721 AN XY: 485018

Gnomad4 AFR exome AF: 0.00122

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.000217

Gnomad4 EAS exome AF: 0.00167

Gnomad4 SAS exome AF: 0.00190

Gnomad4 FIN exome AF: 0.00207

Gnomad4 NFE exome AF: 0.00157

Gnomad4 OTH exome AF: 0.00117

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000974 AC: 121 AN: 124200 Hom.: 0 Cov.: 16 AF XY: 0.00100 AC XY: 59 AN XY: 59024

Gnomad4 AFR AF: 0.00107

Gnomad4 AMR AF: 0.000579

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00233

Gnomad4 SAS AF: 0.00122

Gnomad4 FIN AF: 0.000877

Gnomad4 NFE AF: 0.000998

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000449 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs2303050; hg19: chr19-49535946;