1-160882036-A-T

Position:

• chr1-160882036-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.60 (28412 hom., cov: 31)
  • Exomes 𝑓: 0.67 (330886 hom.)
• Consequence: ITLN1 NM_017625.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ITLN1	NM_017625.3	c.326T>A	p.Val109Asp	missense_variant	4/8	ENST00000326245.4	NP_060095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITLN1	ENST00000326245.4	c.326T>A	p.Val109Asp	missense_variant	4/8	1	NM_017625.3	ENSP00000323587	P1
ITLN1	ENST00000464077.1	n.260T>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90611 AN: 151752 Hom.: 28405 Cov.: 31

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

GnomAD3 exomes AF: 0.660 AC: 165960 AN: 251448 Hom.: 55708 AF XY: 0.661 AC XY: 89832 AN XY: 135906

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 SAS exome AF: 0.631

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.: 83 AF XY: 0.671 AC XY: 487746 AN XY: 727234

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.715

Gnomad4 ASJ exome AF: 0.727

Gnomad4 EAS exome AF: 0.659

Gnomad4 SAS exome AF: 0.628

Gnomad4 FIN exome AF: 0.684

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.660

GnomAD4 genome AF: 0.597 AC: 90657 AN: 151870 Hom.: 28412 Cov.: 31 AF XY: 0.599 AC XY: 44456 AN XY: 74198

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.627

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	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	15
DANN	Benign	0.32
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.058	T
MetaRNN	Benign	0.0000065	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-3.1	N
MutationTaster	Benign	0.98	P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	4.5	N
REVEL	Benign	0.081
Sift	Benign	1.0	T
Sift4G	Benign	0.96	T
Polyphen		0.0	B
Vest4		0.037
MPC		0.19
ClinPred		0.0029	T
GERP RS		4.2
Varity_R		0.18
gMVP		0.63

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

Other links and lift over

dbSNP: rs2274907; hg19: chr1-160851826; COSMIC: COSV58275427; COSMIC: COSV58275427;