chr20-5922871-A-G

Variant names:

• chr20-5922871-A-G
• rs236151
• NM_001819.3:c.727A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001819.3(CHGB):​c.727A>G​(p.Thr243Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,613,678 control chromosomes in the GnomAD database, including 476,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51040 hom., cov: 30)
  • Exomes 𝑓: 0.76 (425647 hom.)
• Consequence: CHGB NM_001819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 31 publications found

Genes affected

CHGB (HGNC:1930): (chromogranin B) This gene encodes a tyrosine-sulfated secretory protein abundant in peptidergic endocrine cells and neurons. This protein may serve as a precursor for regulatory peptides. [provided by RefSeq, Jan 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.3750732E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001819.3. 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
	CHGB	NM_001819.3	MANE Select	c.727A>G	p.Thr243Ala	missense	Exon 4 of 5	NP_001810.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGB	ENST00000378961.9	TSL:1 MANE Select	c.727A>G	p.Thr243Ala	missense	Exon 4 of 5	ENSP00000368244.4
	CHGB	ENST00000966395.1		c.727A>G	p.Thr243Ala	missense	Exon 4 of 5	ENSP00000636454.1
	CHGB	ENST00000886261.1		c.727A>G	p.Thr243Ala	missense	Exon 4 of 5	ENSP00000556320.1

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123848 AN: 151964 Hom.: 50985 Cov.: 30

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.806

GnomAD2 exomes AF: 0.803 AC: 200231 AN: 249462 AF XY: 0.793

Gnomad AFR exome AF: 0.915

Gnomad AMR exome AF: 0.847

Gnomad ASJ exome AF: 0.731

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.831

Gnomad NFE exome AF: 0.752

Gnomad OTH exome AF: 0.780

GnomAD4 exome AF: 0.761 AC: 1112180 AN: 1461596 Hom.: 425647 Cov.: 60 AF XY: 0.760 AC XY: 552776 AN XY: 727068

African (AFR) AF: 0.915 AC: 30640 AN: 33478

American (AMR) AF: 0.843 AC: 37672 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 19154 AN: 26130

East Asian (EAS) AF: 0.998 AC: 39640 AN: 39700

South Asian (SAS) AF: 0.767 AC: 66128 AN: 86240

European-Finnish (FIN) AF: 0.828 AC: 44188 AN: 53346

Middle Eastern (MID) AF: 0.795 AC: 4583 AN: 5768

European-Non Finnish (NFE) AF: 0.741 AC: 823696 AN: 1111860

Other (OTH) AF: 0.770 AC: 46479 AN: 60384

GnomAD4 genome AF: 0.815 AC: 123960 AN: 152082 Hom.: 51040 Cov.: 30 AF XY: 0.820 AC XY: 60941 AN XY: 74322

African (AFR) AF: 0.913 AC: 37887 AN: 41510

American (AMR) AF: 0.813 AC: 12425 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2530 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5129 AN: 5150

South Asian (SAS) AF: 0.772 AC: 3710 AN: 4806

European-Finnish (FIN) AF: 0.843 AC: 8935 AN: 10602

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50746 AN: 67956

Other (OTH) AF: 0.808 AC: 1701 AN: 2104

Alfa AF: 0.765 Hom.: 141195

Bravo AF: 0.820

ESP6500AA AF: 0.907 AC: 3997

ESP6500EA AF: 0.743 AC: 6388

ExAC AF: 0.802 AC: 97324

Asia WGS AF: 0.903 AC: 3140 AN: 3478

EpiCase AF: 0.741

EpiControl AF: 0.738

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.033
DANN	Benign	0.49
DEOGEN2	Benign	0.063	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.34
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.018
Sift	Benign	0.56	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.0090
MPC		0.082
ClinPred		0.0039	T
GERP RS		-3.9
Varity_R		0.034
gMVP		0.11
Mutation Taster		=99/1	polymorphism (auto)

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: rs236151; hg19: chr20-5903517; COSMIC: COSV107500552; COSMIC: COSV107500552;