rs13345685

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-49049004-G-A
• chr19-49049004-G-C

Variant summary

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

The NM_033183.3(CGB8):​c.-265C>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 0.305 in 1,351,002 control chromosomes in the GnomAD database, including 62,100 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 0.32 (7810 hom., cov: 30)
  • Exomes 𝑓: 0.30 (54290 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

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>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_149439.1
	CGB8	NM_033183.3	MANE Select	c.-265C>T		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>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000403649.2	P0DN86-1
	CGB8	ENST00000448456.4	TSL:1 MANE Select	c.-265C>T		5_prime_UTR	Exon 1 of 3	ENSP00000403649.2	P0DN86-1
	CGB8	ENST00000933082.1		c.-265C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000603141.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 48783 AN: 150504 Hom.: 7811 Cov.: 30

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.303 AC: 363768 AN: 1200374 Hom.: 54290 Cov.: 21 AF XY: 0.304 AC XY: 176758 AN XY: 580934

African (AFR) AF: 0.341 AC: 8660 AN: 25422

American (AMR) AF: 0.280 AC: 5163 AN: 18456

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 5084 AN: 17470

East Asian (EAS) AF: 0.319 AC: 10121 AN: 31720

South Asian (SAS) AF: 0.321 AC: 18730 AN: 58424

European-Finnish (FIN) AF: 0.386 AC: 10513 AN: 27222

Middle Eastern (MID) AF: 0.427 AC: 1394 AN: 3264

European-Non Finnish (NFE) AF: 0.297 AC: 288249 AN: 968984

Other (OTH) AF: 0.321 AC: 15854 AN: 49412

GnomAD4 genome AF: 0.324 AC: 48793 AN: 150628 Hom.: 7810 Cov.: 30 AF XY: 0.326 AC XY: 23989 AN XY: 73572

African (AFR) AF: 0.337 AC: 13672 AN: 40572

American (AMR) AF: 0.290 AC: 4401 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3466

East Asian (EAS) AF: 0.316 AC: 1629 AN: 5160

South Asian (SAS) AF: 0.310 AC: 1483 AN: 4790

European-Finnish (FIN) AF: 0.386 AC: 4048 AN: 10480

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.316 AC: 21380 AN: 67706

Other (OTH) AF: 0.323 AC: 676 AN: 2092

Alfa AF: 0.197 Hom.: 388

Bravo AF: 0.317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.44
PhyloP100		-0.23
PromoterAI		-0.011	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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; COSMIC: COSV56822926; COSMIC: COSV56822926;