chr20-5922871-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001819.3(CHGB):​c.727A>T​(p.Thr243Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0418849).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGB	NM_001819.3	MANE Select	c.727A>T	p.Thr243Ser	missense	Exon 4 of 5	NP_001810.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGB	ENST00000378961.9	TSL:1 MANE Select	c.727A>T	p.Thr243Ser	missense	Exon 4 of 5	ENSP00000368244.4
	CHGB	ENST00000455042.1	TSL:3	c.667A>T	p.Thr223Ser	missense	Exon 5 of 5	ENSP00000416643.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249462 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

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: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461654 Hom.: 0 Cov.: 60 AF XY: 0.00000138 AC XY: 1 AN XY: 727104

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111902

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.020
DANN	Benign	0.71
DEOGEN2	Benign	0.060	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.34
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.020
Sift	Benign	0.37	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.084
MutPred		0.40		Gain of glycosylation at T243 (P = 0.1432)
MVP		0.17
MPC		0.091
ClinPred		0.047	T
GERP RS		-3.9
Varity_R		0.035
gMVP		0.077
Mutation Taster		=100/0	polymorphism

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;