Genetic Variant ITLN1:p.Arg313Pro (chr1-160876668-C-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017625.3(ITLN1):c.938G>C(p.Arg313Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,614,102 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 17 hom. )

Consequence

ITLN1
NM_017625.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.642

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013568729).

BP6

Variant 1-160876668-C-G is Benign according to our data. Variant chr1-160876668-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 724321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITLN1	NM_017625.3 link	c.938G>C	p.Arg313Pro	missense_variant	Exon 8 of 8	ENST00000326245.4	NP_060095.2	Q8WWA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITLN1	ENST00000326245.4 link	c.938G>C	p.Arg313Pro	missense_variant	Exon 8 of 8	1	NM_017625.3	ENSP00000323587.3		Q8WWA0

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

466

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00512

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00345

AC:

867

AN:

251224

AF XY:

0.00358

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00527

Gnomad NFE exome

AF:

0.00551

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00399

AC:

5826

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

2792

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.000597

AC:

AN:

33478

American (AMR)

AF:

0.00123

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00165

AC:

142

AN:

86248

European-Finnish (FIN)

AF:

0.00545

AC:

291

AN:

53414

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00459

AC:

5105

AN:

1111938

Other (OTH)

AF:

0.00338

AC:

204

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

298

596

894

1192

1490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00305

AC:

465

AN:

152310

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

217

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

41568

American (AMR)

AF:

0.00157

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00433

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00510

AC:

347

AN:

68020

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00396

Hom.:

Bravo

AF:

0.00273

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00389

AC:

472

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00439

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Uncertain

0.60

Eigen

Benign

-0.75

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.028

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0068

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.85

MutationAssessor

Pathogenic

3.2

PhyloP100

-0.64

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.12

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.43

MVP

0.23

MPC

0.60

ClinPred

0.092

GERP RS

-3.1

Varity_R

0.77

gMVP

0.91

Mutation Taster

=90/10

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-160876668-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over