chr19-49054602-G-A

Variant names:

• chr19-49054602-G-A
• rs932971469
• NM_001385261.1:c.187C>T

Variant summary

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

The NM_001385261.1(CGB7):​c.187C>T​(p.Arg63Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000076 (0 hom., cov: 18)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53
• 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.187C>T	p.Arg63Cys	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.187C>T	p.Arg63Cys	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.187C>T	p.Arg63Cys	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.187C>T	p.Arg63Cys	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.187C>T	p.Arg63Cys	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes AF: 0.00000762 AC: 1 AN: 131200 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000168

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 56778 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000111 AC: 11 AN: 987074 Hom.: 0 Cov.: 15 AF XY: 0.00000813 AC XY: 4 AN XY: 492112

African (AFR) AF: 0.0000390 AC: 1 AN: 25644

American (AMR) AF: 0.0000667 AC: 2 AN: 29966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19078

East Asian (EAS) AF: 0.00 AC: 0 AN: 33698

South Asian (SAS) AF: 0.0000321 AC: 2 AN: 62286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3148

European-Non Finnish (NFE) AF: 0.00000543 AC: 4 AN: 737272

Other (OTH) AF: 0.0000453 AC: 2 AN: 44118

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000762 AC: 1 AN: 131200 Hom.: 0 Cov.: 18 AF XY: 0.0000159 AC XY: 1 AN XY: 62760

African (AFR) AF: 0.00 AC: 0 AN: 36168

American (AMR) AF: 0.00 AC: 0 AN: 13158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3180

East Asian (EAS) AF: 0.00 AC: 0 AN: 4498

South Asian (SAS) AF: 0.00 AC: 0 AN: 3714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.0000168 AC: 1 AN: 59424

Other (OTH) AF: 0.00 AC: 0 AN: 1720

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.187C>T (p.R63C) alteration is located in exon 3 (coding exon 3) of the CGB7 gene. This alteration results from a C to T substitution at nucleotide position 187, causing the arginine (R) at amino acid position 63 to be replaced by a cysteine (C). 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	Pathogenic	0.88
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D;D;D
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.94	D;.;.
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-0.57	T
PhyloP100		2.5
PROVEAN	Uncertain	-2.8	D;.;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.019	D;.;.
Sift4G	Uncertain	0.020	D;D;D
Vest4		0.60
MVP		0.49
MPC		2.5
ClinPred		0.78	D
GERP RS		1.8
Varity_R		0.12
gMVP		0.35
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs932971469; hg19: chr19-49557859;