19-49036845-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033377.2(CGB1):​c.-134C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000355 in 1,127,940 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: 0.0000035 (0 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]

ENSG00000267335 (HGNC:):

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB1	NM_033377.2	c.-134C>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000301407.8	NP_203695.2
CGB1	NM_001382421.1	c.-347C>A		5_prime_UTR_variant	Exon 1 of 3		NP_001369350.1
SNAR-G1	NR_004383.1	n.-175G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB1	ENST00000301407.8	c.-134C>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_033377.2	ENSP00000301407.6
ENSG00000267335	ENST00000591656.1	c.-347C>A		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000466140.1
ENSG00000267335	ENST00000604577.1	c.-134C>A		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000474022.1
CGB1	ENST00000601167.1	c.-347C>A		5_prime_UTR_variant	Exon 1 of 3	5		ENSP00000472896.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000355 AC: 4 AN: 1127940 Hom.: 0 Cov.: 15 AF XY: 0.00000525 AC XY: 3 AN XY: 571582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000520

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.37
DANN	Benign	0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-49540102;