NM_033377.2:c.-134C>G

Variant names:

• chr19-49036845-G-C
• rs34291483
• NM_033377.2:c.-134C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033377.2(CGB1):​c.-134C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 1,127,942 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CGB1 NM_033377.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 0 publications found

Genes affected

CGB1 (HGNC:16721): (chorionic gonadotropin subunit beta 1) 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 CGB1 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 155 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:):

SNAR-G1 (HGNC:34327): (small NF90 (ILF3) associated RNA G1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033377.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB1	NM_033377.2	MANE Select	c.-134C>G		5_prime_UTR	Exon 1 of 3	NP_203695.2	A6NKQ9-2
	CGB1	NM_001382421.1		c.-347C>G		5_prime_UTR	Exon 1 of 3	NP_001369350.1
	SNAR-G1	NR_004383.1		n.-175G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB1	ENST00000301407.8	TSL:1 MANE Select	c.-134C>G		5_prime_UTR	Exon 1 of 3	ENSP00000301407.6	A6NKQ9-2
	ENSG00000267335	ENST00000591656.1	TSL:2	c.-347C>G		5_prime_UTR	Exon 1 of 3	ENSP00000466140.1	K7ELM3
	ENSG00000267335	ENST00000604577.1	TSL:1	c.-134C>G		5_prime_UTR	Exon 1 of 3	ENSP00000474022.1	S4R385

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000177 AC: 2 AN: 1127942 Hom.: 0 Cov.: 15 AF XY: 0.00000350 AC XY: 2 AN XY: 571582

African (AFR) AF: 0.00 AC: 0 AN: 26942

American (AMR) AF: 0.00 AC: 0 AN: 40080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23034

East Asian (EAS) AF: 0.00 AC: 0 AN: 37084

South Asian (SAS) AF: 0.00 AC: 0 AN: 76852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5096

European-Non Finnish (NFE) AF: 0.00000244 AC: 2 AN: 819236

Other (OTH) AF: 0.00 AC: 0 AN: 48884

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.38
DANN	Benign	0.59
PhyloP100		0.65
PromoterAI		0.040	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs34291483; hg19: chr19-49540102;