rs1372088698

Variant names:

• chr19-49054526-C-G
• rs1372088698
• NM_001385261.1:c.263G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-49054526-C-G
• chr19-49054526-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001385261.1(CGB7):​c.263G>C​(p.Arg88Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic 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. R88W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000075 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• 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 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.263G>C	p.Arg88Pro	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.263G>C	p.Arg88Pro	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.263G>C	p.Arg88Pro	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.263G>C	p.Arg88Pro	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.263G>C	p.Arg88Pro	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes AF: 0.00000752 AC: 1 AN: 132990 Hom.: 0 Cov.: 19

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: 0.0000166

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000154 AC: 2 AN: 1300764 Hom.: 0 Cov.: 25 AF XY: 0.00000309 AC XY: 2 AN XY: 646982

⚠️ 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: 31490

American (AMR) AF: 0.00 AC: 0 AN: 38516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24302

East Asian (EAS) AF: 0.00 AC: 0 AN: 37058

South Asian (SAS) AF: 0.00 AC: 0 AN: 79520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3864

European-Non Finnish (NFE) AF: 0.00000203 AC: 2 AN: 984694

Other (OTH) AF: 0.00 AC: 0 AN: 54694

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.044843), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000752 AC: 1 AN: 132990 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 63486

⚠️ 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: 36744

American (AMR) AF: 0.00 AC: 0 AN: 13192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3230

East Asian (EAS) AF: 0.00 AC: 0 AN: 4550

South Asian (SAS) AF: 0.00 AC: 0 AN: 3644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.0000166 AC: 1 AN: 60390

Other (OTH) AF: 0.00 AC: 0 AN: 1704

⚠️ 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.78	D;D;D
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Uncertain	0.95	D;.;.
M_CAP	Pathogenic	0.40	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	-0.057	T
PhyloP100		-0.29
PROVEAN	Uncertain	-4.0	D;.;.
REVEL	Uncertain	0.52
Sift	Uncertain	0.0050	D;.;.
Sift4G	Uncertain	0.050	T;T;T
Vest4		0.66
MVP		0.73
MPC		2.6
ClinPred		0.75	D
GERP RS		1.8
Varity_R		0.70
gMVP		0.43
Mutation Taster		=89/11	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: rs1372088698; hg19: chr19-49557783;