19-49032689-G-T

Variant names:

• chr19-49032689-G-T
• rs2303050
• NM_033378.2:c.177+18G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033378.2(CGB2):​c.177+18G>T 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: not found (cov: 16)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CGB2 NM_033378.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033378.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB2	NM_033378.2	MANE Select	c.177+18G>T		intron	N/A	NP_203696.2
	CGB2	NM_001319065.2		c.141+18G>T		intron	N/A	NP_001305994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB2	ENST00000359342.7	TSL:1 MANE Select	c.177+18G>T		intron	N/A	ENSP00000352295.6
	CGB2	ENST00000474913.1	TSL:1	c.141+18G>T		intron	N/A	ENSP00000471177.1
	ENSG00000267335	ENST00000591656.1	TSL:2	c.-28+3837C>A		intron	N/A	ENSP00000466140.1

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome AF: 0.00000410 AC: 4 AN: 976164 Hom.: 0 Cov.: 15 AF XY: 0.00000412 AC XY: 2 AN XY: 485178

African (AFR) AF: 0.00 AC: 0 AN: 22158

American (AMR) AF: 0.00 AC: 0 AN: 28444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18422

East Asian (EAS) AF: 0.00 AC: 0 AN: 33562

South Asian (SAS) AF: 0.00 AC: 0 AN: 60988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3092

European-Non Finnish (NFE) AF: 0.00000544 AC: 4 AN: 735552

Other (OTH) AF: 0.00 AC: 0 AN: 43560

GnomAD4 genome Cov.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.90
PhyloP100		-1.0

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: rs2303050; hg19: chr19-49535946;