19-49054556-T-C

Variant names:

• chr19-49054556-T-C
• rs1479504138
• NM_001385261.1:c.233A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001385261.1(CGB7):​c.233A>G​(p.Asn78Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. N78T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000030 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0000034 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 2 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21200454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.233A>G	p.Asn78Ser	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.233A>G	p.Asn78Ser	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.233A>G	p.Asn78Ser	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.233A>G	p.Asn78Ser	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.233A>G	p.Asn78Ser	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes AF: 0.0000304 AC: 4 AN: 131528 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.000110

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000330 AC: 2 AN: 60592 AF XY: 0.0000327

Gnomad AFR exome AF: 0.000361

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: 0.00000340 AC: 4 AN: 1177948 Hom.: 0 Cov.: 19 AF XY: 0.00000171 AC XY: 1 AN XY: 585740

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000135 AC: 4 AN: 29604

American (AMR) AF: 0.00 AC: 0 AN: 34644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22594

East Asian (EAS) AF: 0.00 AC: 0 AN: 35046

South Asian (SAS) AF: 0.00 AC: 0 AN: 73016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3620

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 888934

Other (OTH) AF: 0.00 AC: 0 AN: 50548

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000304 AC: 4 AN: 131528 Hom.: 0 Cov.: 19 AF XY: 0.0000478 AC XY: 3 AN XY: 62762

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000110 AC: 4 AN: 36504

American (AMR) AF: 0.00 AC: 0 AN: 13148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3182

East Asian (EAS) AF: 0.00 AC: 0 AN: 4480

South Asian (SAS) AF: 0.00 AC: 0 AN: 3600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 59566

Other (OTH) AF: 0.00 AC: 0 AN: 1696

⚠️ 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	0.097
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.33	T;T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.76	T;.;.
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Uncertain	-0.25	T
PhyloP100		1.7
PROVEAN	Benign	0.090	N;.;.
REVEL	Benign	0.25
Sift	Benign	0.044	D;.;.
Sift4G	Benign	0.098	T;T;T
Vest4		0.13
MVP		0.50
MPC		1.1
ClinPred		0.073	T
GERP RS		0.68
Varity_R		0.050
gMVP		0.080
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1479504138; hg19: chr19-49557813;