Genetic Variant ITLN1:p.Val109Asp (chr1-160882036-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_017625.3(ITLN1):c.326T>A(p.Val109Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 1,613,736 control chromosomes in the GnomAD database, including 359,298 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 0.60 ( 28412 hom., cov: 31)

Exomes 𝑓: 0.67 ( 330886 hom. )

Consequence

ITLN1
NM_017625.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

Publications

91 publications found

Variant links:

Genes affected

ITLN1 (HGNC:18259): (intelectin 1) Enables calcium ion binding activity; identical protein binding activity; and oligosaccharide binding activity. Involved in positive regulation of glucose import; positive regulation of protein phosphorylation; and protein homotrimerization. Located in extracellular exosome. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ITLN1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=6.5004087E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITLN1	NM_017625.3 link	c.326T>A	p.Val109Asp	missense_variant	Exon 4 of 8	ENST00000326245.4	NP_060095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITLN1	ENST00000326245.4 link	c.326T>A	p.Val109Asp	missense_variant	Exon 4 of 8	1	NM_017625.3	ENSP00000323587.3
ITLN1	ENST00000464077.1 link	n.260T>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90611

AN:

151752

Hom.:

28405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.794

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.730

Gnomad EAS

AF:

0.676

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.630

GnomAD2 exomes

AF:

0.660

AC:

165960

AN:

251448

AF XY:

0.661

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.721

Gnomad ASJ exome

AF:

0.733

Gnomad EAS exome

AF:

0.678

Gnomad FIN exome

AF:

0.686

Gnomad NFE exome

AF:

0.676

Gnomad OTH exome

AF:

0.679

GnomAD4 exome

AF:

0.671

AC:

980310

AN:

1461866

Hom.:

330886

Cov.:

AF XY:

0.671

AC XY:

487746

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.367

AC:

12299

AN:

33480

American (AMR)

AF:

0.715

AC:

31993

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.727

AC:

19004

AN:

26136

East Asian (EAS)

AF:

0.659

AC:

26150

AN:

39698

South Asian (SAS)

AF:

0.628

AC:

54186

AN:

86256

European-Finnish (FIN)

AF:

0.684

AC:

36541

AN:

53416

Middle Eastern (MID)

AF:

0.711

AC:

4096

AN:

5762

European-Non Finnish (NFE)

AF:

0.680

AC:

756163

AN:

1112000

Other (OTH)

AF:

0.660

AC:

39878

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

20951

41902

62852

83803

104754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19360

38720

58080

77440

96800

<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:

0.597

AC:

90657

AN:

151870

Hom.:

28412

Cov.:

AF XY:

0.599

AC XY:

44456

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.375

AC:

15512

AN:

41378

American (AMR)

AF:

0.678

AC:

10356

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.730

AC:

2534

AN:

3472

East Asian (EAS)

AF:

0.676

AC:

3475

AN:

5140

South Asian (SAS)

AF:

0.626

AC:

3016

AN:

4818

European-Finnish (FIN)

AF:

0.692

AC:

7286

AN:

10526

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.681

AC:

46237

AN:

67940

Other (OTH)

AF:

0.627

AC:

1324

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1757

3514

5272

7029

8786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.659

Hom.:

10705

Bravo

AF:

0.589

TwinsUK

AF:

0.675

AC:

2502

ALSPAC

AF:

0.663

AC:

2555

ESP6500AA

AF:

0.377

AC:

1660

ESP6500EA

AF:

0.682

AC:

5864

ExAC

AF:

0.648

AC:

78735

Asia WGS

AF:

0.591

AC:

2054

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.070

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.058

MetaRNN

Benign

0.0000065

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-3.1

PhyloP100

1.6

PrimateAI

Benign

0.43

PROVEAN

Benign

4.5

REVEL

Benign

0.081

Sift

Benign

1.0

Sift4G

Benign

0.96

Polyphen

0.0

Vest4

0.037

MPC

0.19

ClinPred

0.0029

GERP RS

4.2

Varity_R

0.18

gMVP

0.63

Mutation Taster

=86/14

polymorphism (auto)

(source)

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

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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