rs745743591

Variant names:

• chr19-49054536-C-G
• rs745743591
• NM_001385261.1:c.253G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-49054536-C-G
• chr19-49054536-C-T

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.253G>C​(p.Glu85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. E85K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 19)
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669
• 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=0.21720508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.253G>C	p.Glu85Gln	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.253G>C	p.Glu85Gln	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.253G>C	p.Glu85Gln	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.253G>C	p.Glu85Gln	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.253G>C	p.Glu85Gln	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Uncertain	0.52	D;D;D
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.67	T;.;.
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.29	T
PhyloP100		0.67
PROVEAN	Benign	-1.6	N;.;.
REVEL	Benign	0.22
Sift	Benign	0.10	T;.;.
Sift4G	Benign	0.41	T;T;T
Vest4		0.14
MVP		0.45
MPC		1.0
ClinPred		0.32	T
GERP RS		1.8
Varity_R		0.069
gMVP		0.18
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs745743591; hg19: chr19-49557793;