19-49054307-G-C

Variant names:

• chr19-49054307-G-C
• rs774968410
• NM_001385261.1:c.482C>G

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.482C>G​(p.Pro161Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000562 in 1,600,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. P161Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.968
• 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: 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=0.088560104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.482C>G	p.Pro161Arg	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.482C>G	p.Pro161Arg	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.482C>G	p.Pro161Arg	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.482C>G	p.Pro161Arg	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.482C>G	p.Pro161Arg	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151350 Hom.: 0 Cov.: 27

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: 0.00000858 AC: 2 AN: 232976 AF XY: 0.0000159

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: 0.00000552 AC: 8 AN: 1449262 Hom.: 0 Cov.: 45 AF XY: 0.00000556 AC XY: 4 AN XY: 719904

⚠️ 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: 33340

American (AMR) AF: 0.00 AC: 0 AN: 44158

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4150

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1105942

Other (OTH) AF: 0.0000334 AC: 2 AN: 59808

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000670), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151350 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 73842

African (AFR) AF: 0.00 AC: 0 AN: 41318

American (AMR) AF: 0.00 AC: 0 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10522

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

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67684

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

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.54	T;.;.
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.97
PROVEAN	Benign	-1.1	N;.;.
REVEL	Benign	0.048
Sift	Benign	0.064	T;.;.
Sift4G	Benign	0.12	T;T;T
Vest4		0.16
MutPred		0.23		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.12
MPC		2.2
ClinPred		0.078	T
GERP RS		-0.68
Varity_R		0.036
gMVP		0.086
Mutation Taster		=98/2	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: rs774968410; hg19: chr19-49557564;