chr1-160876732-C-G

Variant names:

• chr1-160876732-C-G
• NM_017625.3:c.874G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017625.3(ITLN1):​c.874G>C​(p.Gly292Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITLN1 NM_017625.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017625.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITLN1	NM_017625.3	MANE Select	c.874G>C	p.Gly292Arg	missense	Exon 8 of 8	NP_060095.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITLN1	ENST00000326245.4	TSL:1 MANE Select	c.874G>C	p.Gly292Arg	missense	Exon 8 of 8	ENSP00000323587.3	Q8WWA0
	ITLN1	ENST00000896872.1		c.874G>C	p.Gly292Arg	missense	Exon 8 of 8	ENSP00000566931.1
	ITLN1	ENST00000896873.1		c.874G>C	p.Gly292Arg	missense	Exon 8 of 8	ENSP00000566932.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.42
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0026	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		3.5
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.54		Gain of catalytic residue at G292 (P = 0.0634)
MVP		0.47
MPC		0.60
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.93
gMVP		0.79
Mutation Taster		=82/18	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

hg19: chr1-160846522;