19-49032689-G-C

Position:

• 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>C 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 0.0011 (2 hom., cov: 16)
  • Exomes 𝑓: 0.0015 (14 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=-0.93).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 138 AN: 124128 Hom.: 2 Cov.: 16 FAILED QC

Gnomad AFR AF: 0.000633

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00257

Gnomad ASJ AF: 0.000646

Gnomad EAS AF: 0.0128

Gnomad SAS AF: 0.00244

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000271

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.00520 AC: 420 AN: 80802 Hom.: 7 AF XY: 0.00508 AC XY: 212 AN XY: 41706

Gnomad AFR exome AF: 0.00212

Gnomad AMR exome AF: 0.00966

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.0148

Gnomad SAS exome AF: 0.00426

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000611

Gnomad OTH exome AF: 0.00424

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00153 AC: 1498 AN: 976016 Hom.: 14 Cov.: 15 AF XY: 0.00162 AC XY: 784 AN XY: 485102

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.00981

Gnomad4 ASJ exome AF: 0.00418

Gnomad4 EAS exome AF: 0.0152

Gnomad4 SAS exome AF: 0.00320

Gnomad4 FIN exome AF: 0.0000658

Gnomad4 NFE exome AF: 0.000417

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00111 AC: 138 AN: 124206 Hom.: 2 Cov.: 16 AF XY: 0.00132 AC XY: 78 AN XY: 59028

Gnomad4 AFR AF: 0.000631

Gnomad4 AMR AF: 0.00256

Gnomad4 ASJ AF: 0.000646

Gnomad4 EAS AF: 0.0128

Gnomad4 SAS AF: 0.00244

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000271

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.000112 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.96
DANN	Benign	0.70

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;