NM_002185.5:c.801-21A>T

Variant names:

• chr5-35875491-A-T
• rs987106
• NM_002185.5:c.801-21A>T

Variant summary

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

The NM_002185.5(IL7R):​c.801-21A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,562,986 control chromosomes in the GnomAD database, including 215,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21185 hom., cov: 32)
  • Exomes 𝑓: 0.52 (194037 hom.)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.139
• Publications: 36 publications found

Genes affected

IL7R (HGNC:6024): (interleukin 7 receptor) The protein encoded by this gene is a receptor for interleukin 7 (IL7). The function of this receptor requires the interleukin 2 receptor, gamma chain (IL2RG), which is a common gamma chain shared by the receptors of various cytokines, including interleukins 2, 4, 7, 9, and 15. This protein has been shown to play a critical role in V(D)J recombination during lymphocyte development. Defects in this gene may be associated with severe combined immunodeficiency (SCID). Alternatively spliced transcript variants have been found. [provided by RefSeq, Dec 2015]

IL7R Gene-Disease associations (from GenCC):

• immunodeficiency 104

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-35875491-A-T is Benign according to our data. Variant chr5-35875491-A-T is described in ClinVar as Benign. ClinVar VariationId is 1165796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002185.5. 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
	IL7R	NM_002185.5	MANE Select	c.801-21A>T		intron	N/A	NP_002176.2
	IL7R	NM_001437964.1		c.801-21A>T		intron	N/A	NP_001424893.1
	IL7R	NM_001410734.1		c.707-21A>T		intron	N/A	NP_001397663.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	ENST00000303115.8	TSL:1 MANE Select	c.801-21A>T		intron	N/A	ENSP00000306157.3
	IL7R	ENST00000877114.1		c.707-21A>T		intron	N/A	ENSP00000547173.1
	IL7R	ENST00000506850.5	TSL:2	c.707-21A>T		intron	N/A	ENSP00000421207.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79445 AN: 151860 Hom.: 21184 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.489

GnomAD2 exomes AF: 0.488 AC: 121833 AN: 249882 AF XY: 0.494

Gnomad AFR exome AF: 0.562

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.271

Gnomad FIN exome AF: 0.632

Gnomad NFE exome AF: 0.537

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.520 AC: 734085 AN: 1411008 Hom.: 194037 Cov.: 24 AF XY: 0.519 AC XY: 366303 AN XY: 705146

African (AFR) AF: 0.560 AC: 18130 AN: 32396

American (AMR) AF: 0.349 AC: 15533 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 13169 AN: 25834

East Asian (EAS) AF: 0.290 AC: 11438 AN: 39420

South Asian (SAS) AF: 0.456 AC: 38851 AN: 85154

European-Finnish (FIN) AF: 0.631 AC: 33681 AN: 53336

Middle Eastern (MID) AF: 0.457 AC: 2599 AN: 5686

European-Non Finnish (NFE) AF: 0.536 AC: 570995 AN: 1065954

Other (OTH) AF: 0.506 AC: 29689 AN: 58684

GnomAD4 genome AF: 0.523 AC: 79473 AN: 151978 Hom.: 21185 Cov.: 32 AF XY: 0.523 AC XY: 38851 AN XY: 74284

African (AFR) AF: 0.556 AC: 23017 AN: 41420

American (AMR) AF: 0.412 AC: 6286 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1415 AN: 5152

South Asian (SAS) AF: 0.446 AC: 2148 AN: 4812

European-Finnish (FIN) AF: 0.635 AC: 6712 AN: 10570

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36369 AN: 67966

Other (OTH) AF: 0.487 AC: 1027 AN: 2110

Alfa AF: 0.530 Hom.: 3949

Bravo AF: 0.506

Asia WGS AF: 0.412 AC: 1432 AN: 3478

EpiCase AF: 0.526

EpiControl AF: 0.537

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Immunodeficiency 104 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.081
DANN	Benign	0.40
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs987106; hg19: chr5-35875593; COSMIC: COSV57406126;