19-49054551-G-C

Position:

• chr19-49054551-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001385261.1(CGB7):​c.238C>G​(p.Arg80Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 18)
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.282

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35779554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.238C>G	p.Arg80Gly	missense_variant	5/5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.238C>G	p.Arg80Gly	missense_variant	5/5		NP_149133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGB7	ENST00000684222.1	c.238C>G	p.Arg80Gly	missense_variant	5/5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.238C>G	p.Arg80Gly	missense_variant	5/5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.238C>G	p.Arg80Gly	missense_variant	5/5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2024

The c.238C>G (p.R80G) alteration is located in exon 3 (coding exon 3) of the CGB7 gene. This alteration results from a C to G substitution at nucleotide position 238, causing the arginine (R) at amino acid position 80 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Uncertain	0.64	D;D;D
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.80	T;.;.
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Uncertain	0.35	D
PROVEAN	Pathogenic	-4.4	D;.;.
REVEL	Uncertain	0.44
Sift	Benign	0.11	T;.;.
Sift4G	Benign	0.19	T;T;T
Vest4		0.15
MVP		0.66
MPC		2.1
ClinPred		0.39	T
GERP RS		0.62
Varity_R		0.25
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs563761154; hg19: chr19-49557808;