rs34291483

Positions:

• chr19-49036845-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033377.2(CGB1):​c.-134C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,280,174 control chromosomes in the GnomAD database, including 159 homozygotes. 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 0.019 (89 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (70 hom.)
• Consequence: CGB1 NM_033377.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CGB1	NM_033377.2	c.-134C>T		5_prime_UTR_variant	1/3	ENST00000301407.8
CGB1	NM_001382421.1	c.-347C>T		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CGB1	ENST00000301407.8	c.-134C>T		5_prime_UTR_variant	1/3	1	NM_033377.2	P1
CGB1	ENST00000601167.1	c.-347C>T		5_prime_UTR_variant	1/3	5

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2893 AN: 152144 Hom.: 89 Cov.: 31

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.00208 AC: 2350 AN: 1127912 Hom.: 70 Cov.: 15 AF XY: 0.00175 AC XY: 998 AN XY: 571562

Gnomad4 AFR exome AF: 0.0718

Gnomad4 AMR exome AF: 0.00359

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000270

Gnomad4 SAS exome AF: 0.000312

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000537

Gnomad4 OTH exome AF: 0.00403

GnomAD4 genome AF: 0.0191 AC: 2901 AN: 152262 Hom.: 89 Cov.: 31 AF XY: 0.0181 AC XY: 1351 AN XY: 74450

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.00686

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0158 Hom.: 9

Bravo AF: 0.0223

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs34291483; hg19: chr19-49540102;