rs34291483

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-49036845-G-A
• chr19-49036845-G-C
• chr19-49036845-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033377.2(CGB1):​c.-134C>T variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 2 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
CGB1	NM_033377.2	c.-134C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	ENST00000301407.8	NP_203695.2
CGB1	NM_033377.2	c.-134C>T		5_prime_UTR_variant	Exon 1 of 3	ENST00000301407.8	NP_203695.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB1	ENST00000301407.8	c.-134C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	1	NM_033377.2	ENSP00000301407.6
ENSG00000267335	ENST00000591656.1	c.-347C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	2		ENSP00000466140.1
CGB1	ENST00000301407.8	c.-134C>T		5_prime_UTR_variant	Exon 1 of 3	1	NM_033377.2	ENSP00000301407.6
ENSG00000267335	ENST00000591656.1	c.-347C>T		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000466140.1

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

African (AFR) AF: 0.0718 AC: 1934 AN: 26924

American (AMR) AF: 0.00359 AC: 144 AN: 40080

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

East Asian (EAS) AF: 0.0000270 AC: 1 AN: 37084

South Asian (SAS) AF: 0.000312 AC: 24 AN: 76852

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

Middle Eastern (MID) AF: 0.00118 AC: 6 AN: 5096

European-Non Finnish (NFE) AF: 0.0000537 AC: 44 AN: 819228

Other (OTH) AF: 0.00403 AC: 197 AN: 48880

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

African (AFR) AF: 0.0660 AC: 2742 AN: 41528

American (AMR) AF: 0.00686 AC: 105 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68024

Other (OTH) AF: 0.0184 AC: 39 AN: 2114

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
PhyloP100		0.65
PromoterAI		-0.024	Neutral
Mutation Taster		=100/0	polymorphism

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;