rs742710

chr20-5923382-C-Gchr20-5923382-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001819.3(CHGB):c.1238C>G(p.Pro413Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P413L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CHGB NM_001819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033766896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHGB	NM_001819.3	c.1238C>G	p.Pro413Arg	missense_variant	4/5	ENST00000378961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHGB	ENST00000378961.9	c.1238C>G	p.Pro413Arg	missense_variant	4/5	1	NM_001819.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.0040
Dann	Benign	0.44
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.0050
Sift	Benign	0.58	T
Sift4G	Benign	0.12	T
Polyphen		0.0	B
Vest4		0.037
MutPred		0.38		Gain of MoRF binding (P = 0.0033);
MVP		0.30
MPC		0.088
ClinPred		0.068	T
GERP RS		-6.0
Varity_R		0.030
gMVP		0.090

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

LitVar

Other links and lift over

dbSNP: rs742710; hg19: chr20-5904028;