Variant chr1-160876668-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin 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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ITLN1	NM_017625.3 linkuse as main transcript	c.938G>C	p.Arg313Pro	missense_variant	8/8	ENST00000326245.4	NP_060095.2	Q8WWA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITLN1	ENST00000326245.4 linkuse as main transcript	c.938G>C	p.Arg313Pro	missense_variant	8/8	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

GnomAD3 exomes

AF:

0.00345

AC:

867

AN:

251224

Hom.:

AF XY:

0.00358

AC XY:

486

AN XY:

135748

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 SAS exome

AF:

0.00157

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

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00165

Gnomad4 FIN exome

AF:

0.00545

Gnomad4 NFE exome

AF:

0.00459

Gnomad4 OTH exome

AF:

0.00338

GnomAD4 genome

AF:

0.00305

AC:

465

AN:

152310

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

217

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.00510

Gnomad4 OTH

AF:

0.00236

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 31, 2018	- -

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

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

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

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over