chr1-160950641-T-C

Variant names:

• chr1-160950641-T-C
• rs12090411
• NM_080878.3:c.512A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080878.3(ITLN2):​c.512A>G​(p.Gln171Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,614,204 control chromosomes in the GnomAD database, including 427 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (235 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (192 hom.)
• Consequence: ITLN2 NM_080878.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.695
• Publications: 4 publications found

Genes affected

ITLN2 (HGNC:20599): (intelectin 2) Predicted to enable oligosaccharide binding activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002090454).
• BP6: Variant 1-160950641-T-C is Benign according to our data. Variant chr1-160950641-T-C is described in ClinVar as Benign. ClinVar VariationId is 780273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080878.3. 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
	ITLN2	NM_080878.3	MANE Select	c.512A>G	p.Gln171Arg	missense	Exon 5 of 8	NP_543154.1	Q8WWU7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITLN2	ENST00000368029.4	TSL:1 MANE Select	c.512A>G	p.Gln171Arg	missense	Exon 5 of 8	ENSP00000357008.3	Q8WWU7-1
	ITLN2	ENST00000934771.1		c.509A>G	p.Gln170Arg	missense	Exon 5 of 8	ENSP00000604830.1
	ITLN2	ENST00000934772.1		c.422A>G	p.Gln141Arg	missense	Exon 4 of 7	ENSP00000604831.1

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4486 AN: 152216 Hom.: 235 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.00790 AC: 1987 AN: 251362 AF XY: 0.00567

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00486

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00308 AC: 4501 AN: 1461870 Hom.: 192 Cov.: 31 AF XY: 0.00257 AC XY: 1872 AN XY: 727242

African (AFR) AF: 0.106 AC: 3552 AN: 33476

American (AMR) AF: 0.00610 AC: 273 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000406 AC: 35 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.000135 AC: 150 AN: 1111998

Other (OTH) AF: 0.00767 AC: 463 AN: 60394

GnomAD4 genome AF: 0.0295 AC: 4497 AN: 152334 Hom.: 235 Cov.: 32 AF XY: 0.0283 AC XY: 2108 AN XY: 74486

African (AFR) AF: 0.102 AC: 4236 AN: 41566

American (AMR) AF: 0.0123 AC: 189 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68022

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

Alfa AF: 0.00654 Hom.: 77

Bravo AF: 0.0329

ESP6500AA AF: 0.101 AC: 447

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00989 AC: 1201

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.3
DANN	Benign	0.91
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.69
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.094
Sift	Benign	0.31	T
Sift4G	Benign	0.56	T
Polyphen		0.0010	B
Vest4		0.086
MVP		0.14
MPC		0.16
ClinPred		0.0027	T
GERP RS		2.0
Varity_R		0.066
gMVP		0.28
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12090411; hg19: chr1-160920431;