chr13-20721898-G-A

Variant names:

• chr13-20721898-G-A
• rs148881803
• NM_001385224.1:c.553G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385224.1(IL17D):​c.553G>A​(p.Asp185Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D185H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IL17D NM_001385224.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14856926).

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.553G>A	p.Asp185Asn	missense	Exon 2 of 2	NP_001372153.1	Q8TAD2
	IL17D	NM_001385221.1		c.574G>A	p.Asp192Asn	missense	Exon 3 of 3	NP_001372150.1
	IL17D	NM_001385222.1		c.574G>A	p.Asp192Asn	missense	Exon 3 of 3	NP_001372151.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17D	ENST00000682841.1	MANE Select	c.553G>A	p.Asp185Asn	missense	Exon 2 of 2	ENSP00000508385.1	Q8TAD2
	IL17D	ENST00000304920.3	TSL:1	c.553G>A	p.Asp185Asn	missense	Exon 3 of 3	ENSP00000302924.3	Q8TAD2
	IL17D	ENST00000962835.1		c.553G>A	p.Asp185Asn	missense	Exon 3 of 3	ENSP00000632894.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455584 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724254

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111198

Other (OTH) AF: 0.00 AC: 0 AN: 60288

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.082
Sift	Benign	0.17	T
Sift4G	Benign	0.24	T
Polyphen		0.29	B
Vest4		0.081
MutPred		0.16		Loss of stability (P = 0.0535)
MVP		0.73
MPC		0.62
ClinPred		0.37	T
GERP RS		3.7
Varity_R		0.054
gMVP		0.46
Mutation Taster		=90/10	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: rs148881803; hg19: chr13-21296037;