NM_001385261.1:c.327A>C

Variant names:

• chr19-49054462-T-G
• rs780960921
• NM_001385261.1:c.327A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001385261.1(CGB7):​c.327A>C​(p.Gln109His) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q109L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0000090 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.719
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03092575).
• BP6: Variant 19-49054462-T-G is Benign according to our data. Variant chr19-49054462-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3491738.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385261.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB7	NM_001385261.1	MANE Select	c.327A>C	p.Gln109His	missense	Exon 5 of 5	NP_001372190.1	P0DN87
	CGB7	NM_033142.2		c.327A>C	p.Gln109His	missense	Exon 5 of 5	NP_149133.1	P0DN87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB7	ENST00000684222.1	MANE Select	c.327A>C	p.Gln109His	missense	Exon 5 of 5	ENSP00000507822.1	P0DN87
	CGB7	ENST00000596965.5	TSL:2	c.327A>C	p.Gln109His	missense	Exon 5 of 5	ENSP00000469076.1	P0DN87
	CGB7	ENST00000597853.5	TSL:2	c.327A>C	p.Gln109His	missense	Exon 5 of 5	ENSP00000470813.1	P0DN87

Frequencies

GnomAD3 genomes AF: 0.0000140 AC: 2 AN: 142388 Hom.: 0 Cov.: 20

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: 0.0000310

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 91566 AF XY: 0.00

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000899 AC: 13 AN: 1445388 Hom.: 0 Cov.: 34 AF XY: 0.0000111 AC XY: 8 AN XY: 718408

African (AFR) AF: 0.00 AC: 0 AN: 33278

American (AMR) AF: 0.00 AC: 0 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25756

East Asian (EAS) AF: 0.00 AC: 0 AN: 39502

South Asian (SAS) AF: 0.00 AC: 0 AN: 85214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4108

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1101154

Other (OTH) AF: 0.00 AC: 0 AN: 59642

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000140 AC: 2 AN: 142388 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 68628

African (AFR) AF: 0.00 AC: 0 AN: 38946

American (AMR) AF: 0.00 AC: 0 AN: 14048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3372

East Asian (EAS) AF: 0.00 AC: 0 AN: 4782

South Asian (SAS) AF: 0.00 AC: 0 AN: 4080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000310 AC: 2 AN: 64588

Other (OTH) AF: 0.00 AC: 0 AN: 1892

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.7
DANN	Benign	0.10
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.034	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.72
PROVEAN	Benign	1.9	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.10
MVP		0.040
MPC		0.96
ClinPred		0.059	T
GERP RS		-2.9
Varity_R		0.045
gMVP		0.11
Mutation Taster		=91/9	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: rs780960921; hg19: chr19-49557719;