Variant 7-16794973-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006408.4(AGR2):c.441T>C(p.Asn147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,613,576 control chromosomes in the GnomAD database, including 182,388 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 0.38 ( 12741 hom., cov: 33)

Exomes 𝑓: 0.48 ( 169647 hom. )

Consequence

AGR2
NM_006408.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.278

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP7

Synonymous conserved (PhyloP=0.278 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGR2	NM_006408.4 linkuse as main transcript	c.441T>C	p.Asn147=	synonymous_variant	7/8	ENST00000419304.7	NP_006399.1
AGR2	XM_005249581.5 linkuse as main transcript	c.441T>C	p.Asn147=	synonymous_variant	7/8		XP_005249638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
AGR2	ENST00000419304.7 linkuse as main transcript	c.441T>C	p.Asn147=	synonymous_variant	7/8	1	NM_006408.4	ENSP00000391490	P1
AGR2	ENST00000401412.5 linkuse as main transcript	c.441T>C	p.Asn147=	synonymous_variant	7/7	2		ENSP00000386025
AGR2	ENST00000450569.5 linkuse as main transcript	c.231T>C	p.Asn77=	synonymous_variant	4/5	5		ENSP00000414806

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57855

AN:

152078

Hom.:

12737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.464

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.418

GnomAD3 exomes

AF:

0.433

AC:

108759

AN:

251314

Hom.:

24709

AF XY:

0.443

AC XY:

60200

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.437

Gnomad ASJ exome

AF:

0.459

Gnomad EAS exome

AF:

0.291

Gnomad SAS exome

AF:

0.465

Gnomad FIN exome

AF:

0.379

Gnomad NFE exome

AF:

0.493

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.477

AC:

696554

AN:

1461380

Hom.:

169647

Cov.:

AF XY:

0.478

AC XY:

347620

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.445

Gnomad4 ASJ exome

AF:

0.455

Gnomad4 EAS exome

AF:

0.313

Gnomad4 SAS exome

AF:

0.466

Gnomad4 FIN exome

AF:

0.383

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.462

GnomAD4 genome

AF:

0.380

AC:

57875

AN:

152196

Hom.:

12741

Cov.:

AF XY:

0.378

AC XY:

28092

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.464

Gnomad4 EAS

AF:

0.300

Gnomad4 SAS

AF:

0.436

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.494

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.466

Hom.:

13838

Bravo

AF:

0.374

Asia WGS

AF:

0.360

AC:

1254

AN:

3478

EpiCase

AF:

0.498

EpiControl

AF:

0.510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.6

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over