chr19-49054586-A-G

Variant names:

• chr19-49054586-A-G
• rs1167500738
• NM_001385261.1:c.203T>C

Variant summary

Our verdict is Likely benign. The variant received -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. 15/20 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
• 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: Likely_benign. The variant received -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 rank	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.203T>C	p.Val68Ala	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.203T>C	p.Val68Ala	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.203T>C	p.Val68Ala	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.203T>C	p.Val68Ala	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.203T>C	p.Val68Ala	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 17 AN: 129224 Hom.: 0 Cov.: 18

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

GnomAD2 exomes AF: 0.0000346 AC: 2 AN: 57824 AF XY: 0.0000686

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 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

African (AFR) AF: 0.000257 AC: 7 AN: 27270

American (AMR) AF: 0.00 AC: 0 AN: 32028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20244

East Asian (EAS) AF: 0.00 AC: 0 AN: 34076

South Asian (SAS) AF: 0.00 AC: 0 AN: 65996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3340

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 793682

Other (OTH) AF: 0.0000215 AC: 1 AN: 46476

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

African (AFR) AF: 0.000420 AC: 15 AN: 35678

American (AMR) AF: 0.000154 AC: 2 AN: 12976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3154

East Asian (EAS) AF: 0.00 AC: 0 AN: 4410

South Asian (SAS) AF: 0.00 AC: 0 AN: 3620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58658

Other (OTH) AF: 0.00 AC: 0 AN: 1700

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 17, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.38
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
Mutation Taster		=96/4	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: rs1167500738; hg19: chr19-49557843; COSMIC: COSV62281790; COSMIC: COSV62281790;