rs6743376

chr2-113074756-C-A

Variant summary

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

The NM_173161.3(IL1F10):c.152C>A(p.Ala51Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 1,611,940 control chromosomes in the GnomAD database, including 362,567 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 0.69 (36333 hom., cov: 32)
  • Exomes 𝑓: 0.67 (326234 hom.)
• Consequence: IL1F10 NM_173161.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

Genes affected

IL1F10 (HGNC:15552): (interleukin 1 family member 10) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. This cytokine is thought to participate in a network of interleukin 1 family members to regulate adapted and innate immune responses. Two alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.929842E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1F10	NM_173161.3	c.152C>A	p.Ala51Asp	missense_variant	4/5	ENST00000341010.6
IL1F10	NM_032556.6	c.152C>A	p.Ala51Asp	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1F10	ENST00000341010.6	c.152C>A	p.Ala51Asp	missense_variant	4/5	1	NM_173161.3	P1
IL1F10	ENST00000393197.3	c.152C>A	p.Ala51Asp	missense_variant	3/4	1		P1
IL1F10	ENST00000496265.1	n.218C>A		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104642 AN: 151946 Hom.: 36282 Cov.: 32

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.717

GnomAD3 exomes AF: 0.695 AC: 174644 AN: 251366 Hom.: 61196 AF XY: 0.697 AC XY: 94717 AN XY: 135842

Gnomad AFR exome AF: 0.745

Gnomad AMR exome AF: 0.733

Gnomad ASJ exome AF: 0.711

Gnomad EAS exome AF: 0.696

Gnomad SAS exome AF: 0.793

Gnomad FIN exome AF: 0.652

Gnomad NFE exome AF: 0.655

Gnomad OTH exome AF: 0.704

GnomAD4 exome AF: 0.667 AC: 973100 AN: 1459876 Hom.: 326234 Cov.: 45 AF XY: 0.669 AC XY: 486182 AN XY: 726338

Gnomad4 AFR exome AF: 0.745

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.700

Gnomad4 EAS exome AF: 0.715

Gnomad4 SAS exome AF: 0.789

Gnomad4 FIN exome AF: 0.647

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.680

GnomAD4 genome AF: 0.689 AC: 104751 AN: 152064 Hom.: 36333 Cov.: 32 AF XY: 0.691 AC XY: 51340 AN XY: 74336

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.719

Alfa AF: 0.668 Hom.: 50448

Bravo AF: 0.697

TwinsUK AF: 0.659 AC: 2442

ALSPAC AF: 0.644 AC: 2481

ESP6500AA AF: 0.729 AC: 3211

ESP6500EA AF: 0.656 AC: 5640

ExAC AF: 0.693 AC: 84139

Asia WGS AF: 0.770 AC: 2678 AN: 3478

EpiCase AF: 0.666

EpiControl AF: 0.666

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	15
Dann	Benign	0.45
DEOGEN2	Benign	0.0018	T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.026	N
MetaRNN	Benign	7.9e-7	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.5	N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	3.2	N;N
REVEL	Benign	0.034
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.057
MPC		0.043
ClinPred		0.0040	T
GERP RS		3.9
Varity_R		0.053
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6743376; hg19: chr2-113832333; COSMIC: COSV61750738;