14-92934971-T-C

Position:

• chr14-92934971-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001275.4(CHGA):​c.*87T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,175,492 control chromosomes in the GnomAD database, including 317,475 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 0.78 (46967 hom., cov: 32)
  • Exomes 𝑓: 0.72 (270508 hom.)
• Consequence: CHGA NM_001275.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.99

Genes affected

CHGA (HGNC:1929): (chromogranin A) The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. It is found in secretory vesicles of neurons and endocrine cells. This gene product is a precursor to three biologically active peptides; vasostatin, pancreastatin, and parastatin. These peptides act as autocrine or paracrine negative modulators of the neuroendocrine system. Two other peptides, catestatin and chromofungin, have antimicrobial activity and antifungal activity, respectively. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHGA	NM_001275.4	c.*87T>C		3_prime_UTR_variant	8/8	ENST00000216492.10	NP_001266.1
CHGA	NM_001301690.2	c.*87T>C		3_prime_UTR_variant	7/7		NP_001288619.1
CHGA	XM_011536370.3	c.*87T>C		3_prime_UTR_variant	9/9		XP_011534672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHGA	ENST00000216492.10	c.*87T>C		3_prime_UTR_variant	8/8	1	NM_001275.4	ENSP00000216492	P1
CHGA	ENST00000334654.4	c.*87T>C		3_prime_UTR_variant	7/7	1		ENSP00000334023

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118592 AN: 151978 Hom.: 46928 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.724 AC: 741139 AN: 1023396 Hom.: 270508 Cov.: 13 AF XY: 0.727 AC XY: 370849 AN XY: 510108

Gnomad4 AFR exome AF: 0.904

Gnomad4 AMR exome AF: 0.763

Gnomad4 ASJ exome AF: 0.711

Gnomad4 EAS exome AF: 0.949

Gnomad4 SAS exome AF: 0.803

Gnomad4 FIN exome AF: 0.698

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.744

GnomAD4 genome AF: 0.780 AC: 118685 AN: 152096 Hom.: 46967 Cov.: 32 AF XY: 0.781 AC XY: 58065 AN XY: 74368

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.785

Alfa AF: 0.739 Hom.: 5241

Bravo AF: 0.789

Asia WGS AF: 0.886 AC: 3082 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.027
DANN	Benign	0.24

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: rs7610; hg19: chr14-93401316;