dbSNP rs149235072: IL7R:p.Ser51Ser (chr5-35860922-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002185.5(IL7R):c.153G>A(p.Ser51Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,613,122 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 64 hom. )

Consequence

IL7R
NM_002185.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.129

Publications

3 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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

IL7R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-35860922-G-A is Benign according to our data. Variant chr5-35860922-G-A is described in ClinVar as Benign. ClinVar VariationId is 353261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.129 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00135 (205/152240) while in subpopulation SAS AF = 0.0327 (158/4826). AF 95% confidence interval is 0.0286. There are 5 homozygotes in GnomAd4. There are 143 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL7R	NM_002185.5	MANE Select	c.153G>A	p.Ser51Ser	synonymous	Exon 2 of 8	NP_002176.2
IL7R	NM_001437964.1		c.153G>A	p.Ser51Ser	synonymous	Exon 2 of 7	NP_001424893.1
IL7R	NM_001410734.1		c.153G>A	p.Ser51Ser	synonymous	Exon 2 of 7	NP_001397663.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL7R	ENST00000303115.8	TSL:1 MANE Select	c.153G>A	p.Ser51Ser	synonymous	Exon 2 of 8	ENSP00000306157.3	P16871-1
IL7R	ENST00000877114.1		c.153G>A	p.Ser51Ser	synonymous	Exon 2 of 7	ENSP00000547173.1
IL7R	ENST00000506850.5	TSL:2	c.153G>A	p.Ser51Ser	synonymous	Exon 2 of 6	ENSP00000421207.1	P16871-3

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

202

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0323

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00385

AC:

968

AN:

251152

AF XY:

0.00521

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00217

AC:

3177

AN:

1460882

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

2140

AN XY:

726840

show subpopulations

African (AFR)

AF:

0.000688

AC:

AN:

33440

American (AMR)

AF:

0.000112

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26110

East Asian (EAS)

AF:

0.000327

AC:

AN:

39696

South Asian (SAS)

AF:

0.0285

AC:

2462

AN:

86240

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000464

AC:

516

AN:

1111136

Other (OTH)

AF:

0.00247

AC:

149

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

184

368

553

737

921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152240

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41536

American (AMR)

AF:

0.000523

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.0327

AC:

158

AN:

4826

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000376

Hom.:

Bravo

AF:

0.000536

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 104 (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.45

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over