19-49054556-T-G

Variant names:

• chr19-49054556-T-G
• rs1479504138
• NM_001385261.1:c.233A>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.233A>C​(p.Asn78Thr) 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 0.000053 (0 hom., cov: 19)
  • Exomes 𝑓: 0.00065 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1005874).
• BP6: Variant 19-49054556-T-G is Benign according to our data. Variant chr19-49054556-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3143888.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.233A>C	p.Asn78Thr	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.233A>C	p.Asn78Thr	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>C	p.Asn78Thr	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.233A>C	p.Asn78Thr	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.233A>C	p.Asn78Thr	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes AF: 0.0000532 AC: 7 AN: 131528 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000152

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: 0.0000839

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000165 AC: 1 AN: 60592 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000789

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: 0.000649 AC: 764 AN: 1177888 Hom.: 0 Cov.: 19 AF XY: 0.000574 AC XY: 336 AN XY: 585710

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

African (AFR) AF: 0.000709 AC: 21 AN: 29602

American (AMR) AF: 0.000144 AC: 5 AN: 34644

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 7 AN: 22594

East Asian (EAS) AF: 0.0000571 AC: 2 AN: 35046

South Asian (SAS) AF: 0.000247 AC: 18 AN: 73016

European-Finnish (FIN) AF: 0.0000250 AC: 1 AN: 39942

Middle Eastern (MID) AF: 0.00110 AC: 4 AN: 3620

European-Non Finnish (NFE) AF: 0.000770 AC: 684 AN: 888876

Other (OTH) AF: 0.000435 AC: 22 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: 0.0000532 AC: 7 AN: 131528 Hom.: 0 Cov.: 19 AF XY: 0.0000478 AC XY: 3 AN XY: 62762

African (AFR) AF: 0.00 AC: 0 AN: 36504

American (AMR) AF: 0.000152 AC: 2 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: 0.0000839 AC: 5 AN: 59566

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

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

Mar 07, 2024

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	0.098
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	5.3
DANN	Benign	0.65
DEOGEN2	Benign	0.27	T;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.51	T;.;.
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.79	T
PhyloP100		1.7
PROVEAN	Benign	3.0	N;.;.
REVEL	Benign	0.23
Sift	Benign	1.0	T;.;.
Sift4G	Benign	1.0	T;T;T
Vest4		0.19
MVP		0.33
MPC		1.1
ClinPred		0.059	T
GERP RS		0.68
Varity_R		0.053
gMVP		0.088
Mutation Taster		=80/20	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;