19-49049004-G-C

Variant names:

• chr19-49049004-G-C
• rs13345685
• NM_033183.3:c.-265C>G

Variant summary

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

The NM_033183.3(CGB8):​c.-265C>G 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 0.00000368 in 1,358,002 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: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: CGB8 NM_033183.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 4 publications found

Genes affected

CGB8 (HGNC:16453): (chorionic gonadotropin subunit beta 8) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 8 subunit of chorionic gonadotropin (CG). Glycoprotein hormones are heterodimers consisting of a common alpha subunit and an unique beta subunit which confers biological specificity. CG is produced by the trophoblastic cells of the placenta and stimulates the ovaries to synthesize the steroids that are essential for the maintenance of pregnancy. The beta subunit of CG is encoded by 6 genes which are arranged in tandem and inverted pairs on chromosome 19q13.3 and contiguous with the luteinizing hormone beta subunit gene. [provided by RefSeq, Jul 2008]

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=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033183.3. 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
	CGB8	NM_033183.3	MANE Select	c.-265C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_149439.1
	CGB8	NM_033183.3	MANE Select	c.-265C>G		5_prime_UTR	Exon 1 of 3	NP_149439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB8	ENST00000448456.4	TSL:1 MANE Select	c.-265C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000403649.2	P0DN86-1
	CGB8	ENST00000448456.4	TSL:1 MANE Select	c.-265C>G		5_prime_UTR	Exon 1 of 3	ENSP00000403649.2	P0DN86-1
	CGB8	ENST00000933082.1		c.-265C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000603141.1

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150596 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000953

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000248 AC: 3 AN: 1207406 Hom.: 0 Cov.: 21 AF XY: 0.00000171 AC XY: 1 AN XY: 584218

African (AFR) AF: 0.00 AC: 0 AN: 25592

American (AMR) AF: 0.00 AC: 0 AN: 18492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17528

East Asian (EAS) AF: 0.00 AC: 0 AN: 31800

South Asian (SAS) AF: 0.0000171 AC: 1 AN: 58634

European-Finnish (FIN) AF: 0.0000366 AC: 1 AN: 27300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3278

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 975090

Other (OTH) AF: 0.00 AC: 0 AN: 49692

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150596 Hom.: 0 Cov.: 30 AF XY: 0.0000272 AC XY: 2 AN XY: 73502

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

African (AFR) AF: 0.00 AC: 0 AN: 40480

American (AMR) AF: 0.00 AC: 0 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.0000953 AC: 1 AN: 10490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67742

Other (OTH) AF: 0.00 AC: 0 AN: 2074

⚠️ 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: 0.00 Hom.: 388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.34
PhyloP100		-0.23
PromoterAI		-0.022	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: rs13345685; hg19: chr19-49552261;