rs563761154

Variant names:

• chr19-49054551-G-A
• rs563761154
• NM_001385261.1:c.238C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49054551-G-A
• chr19-49054551-G-C
• chr19-49054551-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001385261.1(CGB7):​c.238C>T​(p.Arg80Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R80G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 0 publications found

Genes affected

CGB7 (HGNC:16451): (chorionic gonadotropin subunit beta 7) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 7 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.238C>T	p.Arg80Cys	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.238C>T	p.Arg80Cys	missense_variant	Exon 5 of 5		NP_149133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB7	ENST00000684222.1	c.238C>T	p.Arg80Cys	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.238C>T	p.Arg80Cys	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.238C>T	p.Arg80Cys	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD2 exomes AF: 0.0000164 AC: 1 AN: 61134 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000117 AC: 14 AN: 1201202 Hom.: 0 Cov.: 21 AF XY: 0.00000838 AC XY: 5 AN XY: 596970

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

African (AFR) AF: 0.00 AC: 0 AN: 29966

American (AMR) AF: 0.00 AC: 0 AN: 35060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22864

East Asian (EAS) AF: 0.00 AC: 0 AN: 35278

South Asian (SAS) AF: 0.00 AC: 0 AN: 74130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3646

European-Non Finnish (NFE) AF: 0.0000143 AC: 13 AN: 908126

Other (OTH) AF: 0.0000195 AC: 1 AN: 51386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 18

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D;D;D
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.94	D;.;.
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Uncertain	0.48	D
PhyloP100		0.28
PROVEAN	Pathogenic	-5.9	D;.;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.013	D;D;D
Vest4		0.41
MVP		0.78
MPC		2.5
ClinPred		0.98	D
GERP RS		0.62
Varity_R		0.34
gMVP		0.16
Mutation Taster		=90/10	polymorphism

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: rs563761154; hg19: chr19-49557808;