NM_033377.2:c.227A>C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_033377.2(CGB1):c.227A>C(p.Asn76Thr) 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 0.00022 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00092 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CGB1
NM_033377.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.27

Publications

0 publications found

Variant links:

Genes affected

CGB1 (HGNC:16721): (chorionic gonadotropin subunit beta 1) The beta subunit of chorionic gonadotropin (CGB) is encoded by six highly homologous and structurally similar genes that are arranged in tandem and inverted pairs on chromosome 19q13.3, and contiguous with the luteinizing hormone beta (LHB) subunit gene. The CGB genes are primarily distinguished by differences in the 5' untranscribed region. This gene was originally thought to be one of the two pseudogenes (CGB1 and CGB2) of CGB subunit, however, detection of CGB1 and CGB2 transcripts in vivo, and their presence on the polysomes, suggested that these transcripts are translated. To date, a protein product corresponding to CGB1 has not been isolated. The deduced sequence of the hypothetical protein of 132 aa does not share any similarity with that of functional CGB subunits (PMID:8954017). However, a 155 aa protein, translated from a different frame, is about the same size, and shares 98% identity with other CGB subunits. [provided by RefSeq, Jul 2008]

CGB1 links:

ENSG00000267335 (HGNC:):

ENSG00000267335 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025533944).

BP6

Variant 19-49035851-T-G is Benign according to our data. Variant chr19-49035851-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2380607.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033377.2. 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
	CGB1	NM_033377.2	MANE Select	c.227A>C	p.Asn76Thr	missense	Exon 3 of 3	NP_203695.2	A6NKQ9-2
	CGB1	NM_001382421.1		c.191A>C	p.Asn64Thr	missense	Exon 3 of 3	NP_001369350.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CGB1	ENST00000301407.8	TSL:1 MANE Select	c.227A>C	p.Asn76Thr	missense	Exon 3 of 3	ENSP00000301407.6	A6NKQ9-2
ENSG00000267335	ENST00000591656.1	TSL:2	c.-28+675A>C		intron	N/A	ENSP00000466140.1	K7ELM3
ENSG00000267335	ENST00000604577.1	TSL:1	c.9+852A>C		intron	N/A	ENSP00000474022.1	S4R385

Frequencies

GnomAD3 genomes

AF:

0.000225

AC:

AN:

146662

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000271

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000394

Gnomad SAS

AF:

0.000221

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000345

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000214

AC:

AN:

130716

AF XY:

0.000199

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000341

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000541

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000919

AC:

1254

AN:

1364216

Hom.:

Cov.:

AF XY:

0.000825

AC XY:

557

AN XY:

675178

show subpopulations

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

African (AFR)

AF:

0.000758

AC:

AN:

30350

American (AMR)

AF:

0.000350

AC:

AN:

37140

Ashkenazi Jewish (ASJ)

AF:

0.000164

AC:

AN:

24348

East Asian (EAS)

AF:

0.000704

AC:

AN:

36928

South Asian (SAS)

AF:

0.000359

AC:

AN:

80776

European-Finnish (FIN)

AF:

0.0000229

AC:

AN:

43746

Middle Eastern (MID)

AF:

0.00151

AC:

AN:

3968

European-Non Finnish (NFE)

AF:

0.00106

AC:

1111

AN:

1050226

Other (OTH)

AF:

0.000723

AC:

AN:

56734

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.339

Heterozygous variant carriers

139

208

278

347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000225

AC:

AN:

146782

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

AN XY:

71452

show subpopulations

African (AFR)

AF:

0.0000771

AC:

AN:

38926

American (AMR)

AF:

0.000270

AC:

AN:

14790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.000395

AC:

AN:

5062

South Asian (SAS)

AF:

0.000221

AC:

AN:

4516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000345

AC:

AN:

66704

Other (OTH)

AF:

0.00

AC:

AN:

1986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000961

Hom.:

ExAC

AF:

0.000120

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.2

(source)

DANN

Benign

0.64

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.54

M_CAP

Benign

0.032

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.78

PhyloP100

2.3

PrimateAI

Uncertain

0.75

PROVEAN

Benign

3.0

REVEL

Benign

0.22

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0070

Vest4

0.15

MutPred

0.59

Loss of stability (P = 0.0591)

MVP

0.67

MPC

1.2

ClinPred

0.014

GERP RS

0.68

gMVP

0.11

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over