rs8071

Variant names:

• chr7-16792758-T-A
• rs8071
• NM_006408.4:c.*150A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

AGR2 Gene-Disease associations (from GenCC):

• respiratory infections, recurrent, and failure to thrive with or without diarrhea

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AGR2	NM_006408.4	c.*150A>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000419304.7	NP_006399.1
AGR2	XM_005249581.5	c.*150A>T		3_prime_UTR_variant	Exon 8 of 8		XP_005249638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGR2	ENST00000419304.7	c.*150A>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_006408.4	ENSP00000391490.2
AGR2	ENST00000450569.5	c.*193A>T		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000414806.1

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

African (AFR) AF: 0.153 AC: 2273 AN: 14828

American (AMR) AF: 0.109 AC: 2599 AN: 23788

Ashkenazi Jewish (ASJ) AF: 0.0641 AC: 1067 AN: 16636

East Asian (EAS) AF: 0.324 AC: 10397 AN: 32076

South Asian (SAS) AF: 0.0804 AC: 4062 AN: 50538

European-Finnish (FIN) AF: 0.0760 AC: 3341 AN: 43948

Middle Eastern (MID) AF: 0.0367 AC: 142 AN: 3872

European-Non Finnish (NFE) AF: 0.0408 AC: 15404 AN: 377754

Other (OTH) AF: 0.0746 AC: 2312 AN: 30978

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

African (AFR) AF: 0.150 AC: 6237 AN: 41524

American (AMR) AF: 0.0710 AC: 1086 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0675 AC: 234 AN: 3468

East Asian (EAS) AF: 0.296 AC: 1530 AN: 5164

South Asian (SAS) AF: 0.0849 AC: 410 AN: 4828

European-Finnish (FIN) AF: 0.0795 AC: 842 AN: 10592

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0424 AC: 2882 AN: 68010

Other (OTH) AF: 0.0701 AC: 148 AN: 2110

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
PhyloP100		-0.10
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: rs8071; hg19: chr7-16832382;