rs752113515

Variant names:

• chr19-49054482-C-T
• rs752113515
• NM_001385261.1:c.307G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385261.1(CGB7):​c.307G>A​(p.Ala103Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,569,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000051 (0 hom., cov: 20)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2249822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.307G>A	p.Ala103Thr	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.307G>A	p.Ala103Thr	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.307G>A	p.Ala103Thr	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.307G>A	p.Ala103Thr	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.307G>A	p.Ala103Thr	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes AF: 0.0000505 AC: 7 AN: 138562 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000212

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000633

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000252 AC: 2 AN: 79262 AF XY: 0.0000245

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000134

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: 0.0000252 AC: 36 AN: 1430974 Hom.: 0 Cov.: 33 AF XY: 0.0000239 AC XY: 17 AN XY: 710908

African (AFR) AF: 0.00 AC: 0 AN: 33156

American (AMR) AF: 0.0000688 AC: 3 AN: 43618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25678

East Asian (EAS) AF: 0.00 AC: 0 AN: 39302

South Asian (SAS) AF: 0.00 AC: 0 AN: 84854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4086

European-Non Finnish (NFE) AF: 0.0000294 AC: 32 AN: 1089214

Other (OTH) AF: 0.0000169 AC: 1 AN: 59112

GnomAD4 genome AF: 0.0000505 AC: 7 AN: 138562 Hom.: 0 Cov.: 20 AF XY: 0.0000602 AC XY: 4 AN XY: 66466

African (AFR) AF: 0.00 AC: 0 AN: 37896

American (AMR) AF: 0.000147 AC: 2 AN: 13582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3322

East Asian (EAS) AF: 0.000212 AC: 1 AN: 4720

South Asian (SAS) AF: 0.00 AC: 0 AN: 3854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000633 AC: 4 AN: 63216

Other (OTH) AF: 0.00 AC: 0 AN: 1788

Alfa AF: 0.0000540 Hom.: 0

ExAC AF: 0.0000379 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.307G>A (p.A103T) alteration is located in exon 3 (coding exon 3) of the CGB7 gene. This alteration results from a G to A substitution at nucleotide position 307, causing the alanine (A) at amino acid position 103 to be replaced by a threonine (T). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.36	T;T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.84	T;.;.
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.92	T
PhyloP100		2.4
PROVEAN	Benign	-0.14	N;.;.
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.0040	D;D;D
Vest4		0.23
MVP		0.35
MPC		1.3
ClinPred		0.87	D
GERP RS		0.74
Varity_R		0.17
gMVP		0.081
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: rs752113515; hg19: chr19-49557739; COSMIC: COSV100655123; COSMIC: COSV100655123;