rs8071

Positions:

• chr7-16792758-T-A

Variant summary

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

The NM_006408.4(AGR2):​c.*150A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 746,624 control chromosomes in the GnomAD database, including 3,717 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 0.088 (831 hom., cov: 32)
  • Exomes 𝑓: 0.070 (2886 hom.)
• Consequence: AGR2 NM_006408.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

Genes affected

AGR2 (HGNC:328): (anterior gradient 2, protein disulphide isomerase family member) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, a catalytically active thioredoxin domain, and a C-terminal ER-retention sequence. This protein plays a role in cell migration, cellular transformation and metastasis and is as a p53 inhibitor. As an ER-localized molecular chaperone, it plays a role in the folding, trafficking, and assembly of cysteine-rich transmembrane receptors and the cysteine-rich intestinal gylcoprotein mucin. This gene has been implicated in inflammatory bowel disease and cancer progression. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGR2	NM_006408.4	c.*150A>T		3_prime_UTR_variant	8/8	ENST00000419304.7	NP_006399.1
AGR2	XM_005249581.5	c.*150A>T		3_prime_UTR_variant	8/8		XP_005249638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGR2	ENST00000419304.7	c.*150A>T		3_prime_UTR_variant	8/8	1	NM_006408.4	ENSP00000391490	P1
AGR2	ENST00000450569.5	c.*193A>T		3_prime_UTR_variant	5/5	5		ENSP00000414806

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13394 AN: 152086 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.0851

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0424

Gnomad OTH AF: 0.0718

GnomAD4 exome AF: 0.0700 AC: 41597 AN: 594418 Hom.: 2886 Cov.: 8 AF XY: 0.0692 AC XY: 21605 AN XY: 312044

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0641

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.0804

Gnomad4 FIN exome AF: 0.0760

Gnomad4 NFE exome AF: 0.0408

Gnomad4 OTH exome AF: 0.0746

GnomAD4 genome AF: 0.0881 AC: 13411 AN: 152206 Hom.: 831 Cov.: 32 AF XY: 0.0919 AC XY: 6841 AN XY: 74422

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0675

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.0849

Gnomad4 FIN AF: 0.0795

Gnomad4 NFE AF: 0.0424

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0693 Hom.: 71

Bravo AF: 0.0941

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.39

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: rs8071; hg19: chr7-16832382;