19-49044189-G-C

Variant names:

• chr19-49044189-G-C
• rs12610392
• NM_033043.2:c.-21G>C

Variant summary

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

The NM_033043.2(CGB5):​c.-21G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,499,384 control chromosomes in the GnomAD database, including 54,572 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 0.25 (4026 hom., cov: 30)
  • Exomes 𝑓: 0.28 (50546 hom.)
• Consequence: CGB5 NM_033043.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 9 publications found

Genes affected

CGB5 (HGNC:16452): (chorionic gonadotropin subunit beta 5) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB5	NM_033043.2	c.-21G>C		5_prime_UTR_variant	Exon 1 of 3	ENST00000301408.7	NP_149032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB5	ENST00000301408.7	c.-21G>C		5_prime_UTR_variant	Exon 1 of 3	1	NM_033043.2	ENSP00000301408.5

Frequencies

GnomAD3 genomes AF: 0.251 AC: 36244 AN: 144544 Hom.: 4028 Cov.: 30

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.251

GnomAD2 exomes AF: 0.278 AC: 63617 AN: 228900 AF XY: 0.280

Gnomad AFR exome AF: 0.228

Gnomad AMR exome AF: 0.343

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.157

Gnomad FIN exome AF: 0.195

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.285 AC: 385470 AN: 1354742 Hom.: 50546 Cov.: 54 AF XY: 0.286 AC XY: 192549 AN XY: 672276

African (AFR) AF: 0.229 AC: 6880 AN: 30040

American (AMR) AF: 0.343 AC: 14530 AN: 42378

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 7975 AN: 24692

East Asian (EAS) AF: 0.161 AC: 5909 AN: 36598

South Asian (SAS) AF: 0.322 AC: 24642 AN: 76480

European-Finnish (FIN) AF: 0.203 AC: 9615 AN: 47256

Middle Eastern (MID) AF: 0.227 AC: 1193 AN: 5246

European-Non Finnish (NFE) AF: 0.289 AC: 299363 AN: 1036002

Other (OTH) AF: 0.274 AC: 15363 AN: 56050

GnomAD4 genome AF: 0.251 AC: 36262 AN: 144642 Hom.: 4026 Cov.: 30 AF XY: 0.250 AC XY: 17645 AN XY: 70638

African (AFR) AF: 0.229 AC: 8596 AN: 37458

American (AMR) AF: 0.318 AC: 4687 AN: 14726

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1094 AN: 3402

East Asian (EAS) AF: 0.149 AC: 730 AN: 4914

South Asian (SAS) AF: 0.293 AC: 1348 AN: 4594

European-Finnish (FIN) AF: 0.164 AC: 1693 AN: 10326

Middle Eastern (MID) AF: 0.205 AC: 59 AN: 288

European-Non Finnish (NFE) AF: 0.263 AC: 17341 AN: 66034

Other (OTH) AF: 0.247 AC: 497 AN: 2010

Alfa AF: 0.185 Hom.: 433

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.86
DANN	Benign	0.77
PhyloP100		-1.4
PromoterAI		0.037	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12610392; hg19: chr19-49547446; COSMIC: COSV56822465; COSMIC: COSV56822465;