rs142903731

Variant names:

• chr19-49054326-G-A
• rs142903731
• NM_001385261.1:c.463C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49054326-G-A
• chr19-49054326-G-C
• chr19-49054326-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001385261.1(CGB7):​c.463C>T​(p.Pro155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000087 in 1,610,078 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. 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. P155A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052639842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.463C>T	p.Pro155Ser	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.463C>T	p.Pro155Ser	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.463C>T	p.Pro155Ser	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.463C>T	p.Pro155Ser	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.463C>T	p.Pro155Ser	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 150954 Hom.: 0 Cov.: 22

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000846 AC: 2 AN: 236290 AF XY: 0.00

Gnomad AFR exome AF: 0.000133

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: 0.00000891 AC: 13 AN: 1459124 Hom.: 0 Cov.: 35 AF XY: 0.00000827 AC XY: 6 AN XY: 725790

African (AFR) AF: 0.0000299 AC: 1 AN: 33410

American (AMR) AF: 0.0000224 AC: 1 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4204

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111430

Other (OTH) AF: 0.0000166 AC: 1 AN: 60182

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 150954 Hom.: 0 Cov.: 22 AF XY: 0.0000136 AC XY: 1 AN XY: 73602

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

African (AFR) AF: 0.00 AC: 0 AN: 41240

American (AMR) AF: 0.00 AC: 0 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67540

Other (OTH) AF: 0.00 AC: 0 AN: 2062

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.000332 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.5
DANN	Benign	0.76
DEOGEN2	Benign	0.0090	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.80	T;.;.
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.053	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.27
PROVEAN	Benign	-0.11	N;.;.
REVEL	Benign	0.034
Sift	Benign	0.076	T;.;.
Sift4G	Benign	0.087	T;T;T
Vest4		0.15
MVP		0.061
MPC		1.2
ClinPred		0.029	T
GERP RS		-1.1
Varity_R		0.020
gMVP		0.13
Mutation Taster		=100/0	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: rs142903731; hg19: chr19-49557583; COSMIC: COSV62281734; COSMIC: COSV62281734;