dbSNP rs35930240: CGB8:c.-72T>A (chr19-49048811-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_033183.3(CGB8):c.-72T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,611,774 control chromosomes in the GnomAD database, including 1,249 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.037 ( 125 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1124 hom. )

Consequence

CGB8
NM_033183.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.14

Publications

5 publications found

Variant links:

Genes affected

CGB8 (HGNC:16453): (chorionic gonadotropin subunit beta 8) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 8 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]

CGB8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0372 (5623/151298) while in subpopulation AFR AF = 0.0405 (1646/40670). AF 95% confidence interval is 0.0388. There are 125 homozygotes in GnomAd4. There are 2708 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 125 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB8	NM_033183.3 link	c.-72T>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000448456.4	NP_149439.1	P0DN86-1A0A0F7RQP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB8	ENST00000448456.4 link	c.-72T>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_033183.3	ENSP00000403649.2		P0DN86-1

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

5613

AN:

151180

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0403

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0302

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.00541

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.0439

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0400

Gnomad OTH

AF:

0.0342

GnomAD4 exome

AF:

0.0351

AC:

51255

AN:

1460476

Hom.:

1124

Cov.:

AF XY:

0.0348

AC XY:

25314

AN XY:

726640

show subpopulations

African (AFR)

AF:

0.0411

AC:

1351

AN:

32836

American (AMR)

AF:

0.0221

AC:

986

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0250

AC:

652

AN:

26126

East Asian (EAS)

AF:

0.00350

AC:

139

AN:

39696

South Asian (SAS)

AF:

0.0209

AC:

1801

AN:

86230

European-Finnish (FIN)

AF:

0.0480

AC:

2565

AN:

53398

Middle Eastern (MID)

AF:

0.0356

AC:

205

AN:

5752

European-Non Finnish (NFE)

AF:

0.0373

AC:

41495

AN:

1111432

Other (OTH)

AF:

0.0342

AC:

2061

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

2738

5476

8215

10953

13691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1498

2996

4494

5992

7490

<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

AF:

0.0372

AC:

5623

AN:

151298

Hom.:

125

Cov.:

AF XY:

0.0366

AC XY:

2708

AN XY:

73956

show subpopulations

African (AFR)

AF:

0.0405

AC:

1646

AN:

40670

American (AMR)

AF:

0.0301

AC:

460

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

AN:

3472

East Asian (EAS)

AF:

0.00542

AC:

AN:

5166

South Asian (SAS)

AF:

0.0226

AC:

109

AN:

4818

European-Finnish (FIN)

AF:

0.0439

AC:

465

AN:

10594

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0400

AC:

2719

AN:

68008

Other (OTH)

AF:

0.0353

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

265

529

794

1058

1323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0405

Hom.:

Bravo

AF:

0.0365

Asia WGS

AF:

0.0430

AC:

149

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.20

(source)

DANN

Benign

0.74

PhyloP100

-2.1

PromoterAI

-0.0054

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over