rs2303050

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-49032689-G-A
• chr19-49032689-G-C
• chr19-49032689-G-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>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
• 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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB2	NM_033378.2	c.177+18G>A		intron_variant	Intron 2 of 2	ENST00000359342.7	NP_203696.2
CGB2	NM_001319065.2	c.141+18G>A		intron_variant	Intron 2 of 2		NP_001305994.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000967 AC: 120 AN: 124122 Hom.: 0 Cov.: 16

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

GnomAD2 exomes AF: 0.00175 AC: 141 AN: 80802 AF XY: 0.00180

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 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

African (AFR) AF: 0.00122 AC: 27 AN: 22144

American (AMR) AF: 0.00134 AC: 38 AN: 28432

Ashkenazi Jewish (ASJ) AF: 0.000217 AC: 4 AN: 18416

East Asian (EAS) AF: 0.00167 AC: 56 AN: 33556

South Asian (SAS) AF: 0.00190 AC: 116 AN: 60956

European-Finnish (FIN) AF: 0.00207 AC: 63 AN: 30366

Middle Eastern (MID) AF: 0.000971 AC: 3 AN: 3090

European-Non Finnish (NFE) AF: 0.00157 AC: 1154 AN: 735296

Other (OTH) AF: 0.00117 AC: 51 AN: 43540

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

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

African (AFR) AF: 0.00107 AC: 34 AN: 31700

American (AMR) AF: 0.000579 AC: 7 AN: 12094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3096

East Asian (EAS) AF: 0.00233 AC: 10 AN: 4298

South Asian (SAS) AF: 0.00122 AC: 4 AN: 3276

European-Finnish (FIN) AF: 0.000877 AC: 7 AN: 7980

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

European-Non Finnish (NFE) AF: 0.000998 AC: 59 AN: 59124

Other (OTH) AF: 0.00 AC: 0 AN: 1582

⚠️ 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: 0.000449 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
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;