rs370631307

Variant names:

• chr1-160881206-G-A
• rs370631307
• NM_017625.3:c.512C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-160881206-G-A
• chr1-160881206-G-C
• chr1-160881206-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_017625.3(ITLN1):​c.512C>T​(p.Thr171Met) variant causes a missense change. The variant allele was found at a frequency of 0.000224 in 1,613,530 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: ITLN1 NM_017625.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.94
• Publications: 4 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.937
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITLN1	NM_017625.3	c.512C>T	p.Thr171Met	missense_variant	Exon 5 of 8	ENST00000326245.4	NP_060095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITLN1	ENST00000326245.4	c.512C>T	p.Thr171Met	missense_variant	Exon 5 of 8	1	NM_017625.3	ENSP00000323587.3
ITLN1	ENST00000464077.1	n.446C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
ITLN1	ENST00000487531.1	n.316C>T		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152186 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000120 AC: 30 AN: 250760 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000231 AC: 338 AN: 1461344 Hom.: 2 Cov.: 33 AF XY: 0.000232 AC XY: 169 AN XY: 726966

African (AFR) AF: 0.0000897 AC: 3 AN: 33460

American (AMR) AF: 0.0000671 AC: 3 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39676

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86170

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000269 AC: 299 AN: 1111694

Other (OTH) AF: 0.000232 AC: 14 AN: 60382

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152186 Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 11 AN XY: 74330

African (AFR) AF: 0.000121 AC: 5 AN: 41432

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000185 Hom.: 0

Bravo AF: 0.000128

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.000328

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.512C>T (p.T171M) alteration is located in exon 5 (coding exon 4) of the ITLN1 gene. This alteration results from a C to T substitution at nucleotide position 512, causing the threonine (T) at amino acid position 171 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		4.9
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MVP		0.73
MPC		0.57
ClinPred		0.91	D
GERP RS		4.0
Varity_R		0.77
gMVP		0.79
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs370631307; hg19: chr1-160850996; COSMIC: COSV104397671;