19-49032689-G-C

Variant names:

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

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>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
• Publications: 1 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=-0.93).

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>C		intron	N/A	NP_203696.2
	CGB2	NM_001319065.2		c.141+18G>C		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>C		intron	N/A	ENSP00000352295.6
	CGB2	ENST00000474913.1	TSL:1	c.141+18G>C		intron	N/A	ENSP00000471177.1
	ENSG00000267335	ENST00000591656.1	TSL:2	c.-28+3837C>G		intron	N/A	ENSP00000466140.1

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 138 AN: 124128 Hom.: 2 Cov.: 16

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

GnomAD2 exomes AF: 0.00520 AC: 420 AN: 80802 AF XY: 0.00508

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00158 AC: 35 AN: 22156

American (AMR) AF: 0.00981 AC: 279 AN: 28432

Ashkenazi Jewish (ASJ) AF: 0.00418 AC: 77 AN: 18418

East Asian (EAS) AF: 0.0152 AC: 510 AN: 33542

South Asian (SAS) AF: 0.00320 AC: 195 AN: 60946

European-Finnish (FIN) AF: 0.0000658 AC: 2 AN: 30386

Middle Eastern (MID) AF: 0.00259 AC: 8 AN: 3092

European-Non Finnish (NFE) AF: 0.000417 AC: 307 AN: 735488

Other (OTH) AF: 0.00195 AC: 85 AN: 43556

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000631 AC: 20 AN: 31716

American (AMR) AF: 0.00256 AC: 31 AN: 12090

Ashkenazi Jewish (ASJ) AF: 0.000646 AC: 2 AN: 3098

East Asian (EAS) AF: 0.0128 AC: 55 AN: 4296

South Asian (SAS) AF: 0.00244 AC: 8 AN: 3276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 262

European-Non Finnish (NFE) AF: 0.000271 AC: 16 AN: 59126

Other (OTH) AF: 0.00380 AC: 6 AN: 1578

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000112 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.96
DANN	Benign	0.70
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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;