rs6780995

Positions:

• chr3-57104391-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017563.5(IL17RD):​c.764C>T​(p.Thr255Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,602,056 control chromosomes in the GnomAD database, including 372,548 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.63 (31279 hom., cov: 32)
  • Exomes 𝑓: 0.68 (341269 hom.)
• Consequence: IL17RD NM_017563.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.888

Genes affected

IL17RD (HGNC:17616): (interleukin 17 receptor D) This gene encodes a membrane protein belonging to the interleukin-17 receptor (IL-17R) protein family. The encoded protein is a component of the interleukin-17 receptor signaling complex, and the interaction between this protein and IL-17R does not require the interleukin. The gene product also affects fibroblast growth factor signaling, inhibiting or stimulating growth through MAPK/ERK signaling. Alternate splicing generates multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.384437E-6).
• BP6: Variant 3-57104391-G-A is Benign according to our data. Variant chr3-57104391-G-A is described in ClinVar as [Benign]. Clinvar id is 1183074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RD	NM_017563.5	c.764C>T	p.Thr255Met	missense_variant	8/13	ENST00000296318.12	NP_060033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RD	ENST00000296318.12	c.764C>T	p.Thr255Met	missense_variant	8/13	1	NM_017563.5	ENSP00000296318	P1
IL17RD	ENST00000320057.9	c.332C>T	p.Thr111Met	missense_variant	9/14	1		ENSP00000322250
IL17RD	ENST00000463523.5	c.332C>T	p.Thr111Met	missense_variant	8/13	1		ENSP00000417516
IL17RD	ENST00000469841.5	n.701C>T		non_coding_transcript_exon_variant	8/12	2

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95726 AN: 151924 Hom.: 31272 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.619

GnomAD3 exomes AF: 0.619 AC: 152198 AN: 246056 Hom.: 50553 AF XY: 0.631 AC XY: 83690 AN XY: 132684

Gnomad AFR exome AF: 0.571

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.654

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.718

Gnomad FIN exome AF: 0.738

Gnomad NFE exome AF: 0.695

Gnomad OTH exome AF: 0.652

GnomAD4 exome AF: 0.677 AC: 981949 AN: 1450014 Hom.: 341269 Cov.: 32 AF XY: 0.679 AC XY: 489529 AN XY: 721244

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.715

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.703

Gnomad4 OTH exome AF: 0.658

GnomAD4 genome AF: 0.630 AC: 95771 AN: 152042 Hom.: 31279 Cov.: 32 AF XY: 0.628 AC XY: 46633 AN XY: 74306

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.617

Alfa AF: 0.663 Hom.: 72585

Bravo AF: 0.610

TwinsUK AF: 0.708 AC: 2626

ALSPAC AF: 0.709 AC: 2733

ESP6500AA AF: 0.585 AC: 2576

ESP6500EA AF: 0.708 AC: 6087

ExAC AF: 0.624 AC: 75766

Asia WGS AF: 0.416 AC: 1453 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Hypogonadotropic hypogonadism 18 with or without anosmia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.044	T;.;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.82	T;.;.;T
MetaRNN	Benign	0.0000024	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;.;.
MutationTaster	Benign	0.79	P;P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.17	N;N;N;.
REVEL	Benign	0.045
Sift	Benign	0.094	T;T;T;.
Sift4G	Benign	0.30	T;T;T;.
Polyphen		0.66	P;.;.;.
Vest4		0.19
MPC		0.24
ClinPred		0.017	T
GERP RS		-0.52
Varity_R		0.018
gMVP		0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs6780995; hg19: chr3-57138419; COSMIC: COSV56335199; COSMIC: COSV56335199;