chr19-49054586-A-G

Position:

• chr19-49054586-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001385261.1(CGB7):​c.203T>C​(p.Val68Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0000076 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.378

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06835601).
• BP6: Variant 19-49054586-A-G is Benign according to our data. Variant chr19-49054586-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2308382.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.203T>C	p.Val68Ala	missense_variant	5/5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.203T>C	p.Val68Ala	missense_variant	5/5		NP_149133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGB7	ENST00000684222.1	c.203T>C	p.Val68Ala	missense_variant	5/5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.203T>C	p.Val68Ala	missense_variant	5/5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.203T>C	p.Val68Ala	missense_variant	5/5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 17 AN: 129224 Hom.: 0 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.000422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000154

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000346 AC: 2 AN: 57824 Hom.: 0 AF XY: 0.0000686 AC XY: 2 AN XY: 29150

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000757 AC: 8 AN: 1057080 Hom.: 0 Cov.: 17 AF XY: 0.00000570 AC XY: 3 AN XY: 525860

Gnomad4 AFR exome AF: 0.000257

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000215

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000131 AC: 17 AN: 129322 Hom.: 0 Cov.: 18 AF XY: 0.000129 AC XY: 8 AN XY: 61800

Gnomad4 AFR AF: 0.000420

Gnomad4 AMR AF: 0.000154

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.26
DANN	Benign	0.34
DEOGEN2	Benign	0.25	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00065	N
LIST_S2	Benign	0.46	T;.;.
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.068	T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	0.84	N;.;.
REVEL	Benign	0.028
Sift	Benign	0.82	T;.;.
Sift4G	Benign	0.70	T;T;T
Vest4		0.059
MVP		0.048
MPC		1.2
ClinPred		0.014	T
GERP RS		-0.49
Varity_R		0.019
gMVP		0.092

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

Publications

LitVar

Other links and lift over

dbSNP: rs1167500738; hg19: chr19-49557843; COSMIC: COSV62281790; COSMIC: COSV62281790;