chr13-20704078-C-T

Variant names:

• chr13-20704078-C-T
• rs918604752
• NM_001385224.1:c.77C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001385224.1(IL17D):​c.77C>T​(p.Ala26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,118,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A26T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: IL17D NM_001385224.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.483
• Publications: 0 publications found

Genes affected

IL17D (HGNC:5984): (interleukin 17D) The protein encoded by this gene is a cytokine that shares the sequence similarity with IL17. The treatment of endothelial cells with this cytokine has been shown to stimulate the production of other cytokines including IL6, IL8 and CSF2/ GM-CSF. The increased expression of IL8 induced by this cytokine was found to be NF-kappa B-dependent. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.1053409).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385224.1. 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
	IL17D	NM_001385224.1	MANE Select	c.77C>T	p.Ala26Val	missense	Exon 1 of 2	NP_001372153.1	Q8TAD2
	IL17D	NM_001385221.1		c.98C>T	p.Ala33Val	missense	Exon 2 of 3	NP_001372150.1
	IL17D	NM_001385222.1		c.98C>T	p.Ala33Val	missense	Exon 2 of 3	NP_001372151.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17D	ENST00000682841.1	MANE Select	c.77C>T	p.Ala26Val	missense	Exon 1 of 2	ENSP00000508385.1	Q8TAD2
	IL17D	ENST00000304920.3	TSL:1	c.77C>T	p.Ala26Val	missense	Exon 2 of 3	ENSP00000302924.3	Q8TAD2
	IL17D	ENST00000962835.1		c.77C>T	p.Ala26Val	missense	Exon 2 of 3	ENSP00000632894.1

Frequencies

GnomAD3 genomes AF: 0.000188 AC: 27 AN: 143324 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000385

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000149 AC: 1 AN: 6714 AF XY: 0.000217

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: 0.00

Gnomad NFE exome AF: 0.000319

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000271 AC: 264 AN: 974934 Hom.: 0 Cov.: 30 AF XY: 0.000284 AC XY: 132 AN XY: 464354

African (AFR) AF: 0.00 AC: 0 AN: 18764

American (AMR) AF: 0.000206 AC: 1 AN: 4858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9380

East Asian (EAS) AF: 0.00 AC: 0 AN: 14218

South Asian (SAS) AF: 0.00 AC: 0 AN: 21100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2332

European-Non Finnish (NFE) AF: 0.000285 AC: 244 AN: 855402

Other (OTH) AF: 0.000538 AC: 19 AN: 35330

GnomAD4 genome AF: 0.000188 AC: 27 AN: 143324 Hom.: 0 Cov.: 27 AF XY: 0.000157 AC XY: 11 AN XY: 69880

African (AFR) AF: 0.0000507 AC: 2 AN: 39434

American (AMR) AF: 0.00 AC: 0 AN: 14628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3364

East Asian (EAS) AF: 0.00 AC: 0 AN: 4678

South Asian (SAS) AF: 0.00 AC: 0 AN: 4626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000385 AC: 25 AN: 64992

Other (OTH) AF: 0.00 AC: 0 AN: 1978

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.000159

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	Benign	0.16
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.48
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.072
Sift	Benign	0.30	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.057
MutPred		0.48		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.38
MPC		0.58
ClinPred		0.029	T
GERP RS		1.8
PromoterAI		-0.012	Neutral
Varity_R		0.075
gMVP		0.36
Mutation Taster		=94/6	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: rs918604752; hg19: chr13-21278217; COSMIC: COSV105894729; COSMIC: COSV105894729;