rs8102901

Variant names:

• chr19-49049297-C-A
• rs8102901
• NM_033183.3:c.-558G>T

Variant summary

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

The NM_033183.3(CGB8):​c.-558G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 149,414 control chromosomes in the GnomAD database, including 7,996 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 0.33 (7996 hom., cov: 31)
• Consequence: CGB8 NM_033183.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB8	NM_033183.3	c.-558G>T		upstream_gene_variant		ENST00000448456.4	NP_149439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB8	ENST00000448456.4	c.-558G>T		upstream_gene_variant		1	NM_033183.3	ENSP00000403649.2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 48812 AN: 149290 Hom.: 7995 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 48820 AN: 149414 Hom.: 7996 Cov.: 31 AF XY: 0.329 AC XY: 24055 AN XY: 73064

African (AFR) AF: 0.357 AC: 14037 AN: 39338

American (AMR) AF: 0.289 AC: 4393 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1012 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1618 AN: 5140

South Asian (SAS) AF: 0.310 AC: 1489 AN: 4804

European-Finnish (FIN) AF: 0.382 AC: 4008 AN: 10502

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21105 AN: 67690

Other (OTH) AF: 0.323 AC: 667 AN: 2066

Alfa AF: 0.337 Hom.: 1083

Bravo AF: 0.324

Asia WGS AF: 0.290 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.69
PhyloP100		-0.76
PromoterAI		0.053	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8102901; hg19: chr19-49552554;