Genetic Variant AVPI1:p.Ala41Gly (chr10-97679784-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021732.3(AVPI1):c.122C>G(p.Ala41Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,232 control chromosomes in the GnomAD database, including 148,052 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 18234 hom., cov: 32)

Exomes 𝑓: 0.42 ( 129818 hom. )

Consequence

AVPI1
NM_021732.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57

Publications

28 publications found

Variant links:

Genes affected

AVPI1 (HGNC:30898): (arginine vasopressin induced 1) Predicted to act upstream of or within positive regulation of MAPK cascade. [provided by Alliance of Genome Resources, Apr 2022]

AVPI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6955511E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPI1	NM_021732.3 link	c.122C>G	p.Ala41Gly	missense_variant	Exon 2 of 3	ENST00000370626.4	NP_068378.2	Q5T686
AVPI1	XM_017016494.2 link	c.122C>G	p.Ala41Gly	missense_variant	Exon 2 of 3		XP_016871983.1	Q5T686

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPI1	ENST00000370626.4 link	c.122C>G	p.Ala41Gly	missense_variant	Exon 2 of 3	1	NM_021732.3	ENSP00000359660.3		Q5T686

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

71980

AN:

151940

Hom.:

18187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.659

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.357

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.436

GnomAD2 exomes

AF:

0.430

AC:

107343

AN:

249424

AF XY:

0.429

show subpopulations

Gnomad AFR exome

AF:

0.656

Gnomad AMR exome

AF:

0.441

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.505

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.385

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.418

AC:

610495

AN:

1461174

Hom.:

129818

Cov.:

AF XY:

0.420

AC XY:

304937

AN XY:

726884

show subpopulations

African (AFR)

AF:

0.669

AC:

22377

AN:

33466

American (AMR)

AF:

0.440

AC:

19611

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

8640

AN:

26126

East Asian (EAS)

AF:

0.501

AC:

19879

AN:

39664

South Asian (SAS)

AF:

0.509

AC:

43846

AN:

86208

European-Finnish (FIN)

AF:

0.363

AC:

19316

AN:

53166

Middle Eastern (MID)

AF:

0.376

AC:

2171

AN:

5768

European-Non Finnish (NFE)

AF:

0.404

AC:

448663

AN:

1111780

Other (OTH)

AF:

0.430

AC:

25992

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

23229

46459

69688

92918

116147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14164

28328

42492

56656

70820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.474

AC:

72092

AN:

152058

Hom.:

18234

Cov.:

AF XY:

0.472

AC XY:

35056

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.660

AC:

27363

AN:

41482

American (AMR)

AF:

0.420

AC:

6422

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

1156

AN:

3472

East Asian (EAS)

AF:

0.491

AC:

2531

AN:

5160

South Asian (SAS)

AF:

0.495

AC:

2379

AN:

4808

European-Finnish (FIN)

AF:

0.357

AC:

3782

AN:

10584

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.399

AC:

27082

AN:

67946

Other (OTH)

AF:

0.437

AC:

922

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1883

3766

5649

7532

9415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.409

Hom.:

9768

Bravo

AF:

0.486

TwinsUK

AF:

0.402

AC:

1492

ALSPAC

AF:

0.403

AC:

1555

ESP6500AA

AF:

0.646

AC:

2846

ESP6500EA

AF:

0.396

AC:

3408

ExAC

AF:

0.436

AC:

52939

Asia WGS

AF:

0.510

AC:

1775

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0016

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.13

MetaRNN

Benign

0.000017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PhyloP100

1.6

PrimateAI

Benign

0.44

PROVEAN

Benign

0.87

REVEL

Benign

0.10

Sift

Benign

1.0

Sift4G

Benign

0.77

Polyphen

0.0

Vest4

0.044

MPC

0.023

ClinPred

0.0050

GERP RS

5.1

Varity_R

0.067

gMVP

0.18

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over