dbSNP rs1051922: IFNB1:p.Tyr51Tyr (chr9-21077717-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002176.4(IFNB1):c.153C>T(p.Tyr51Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,613,308 control chromosomes in the GnomAD database, including 92,102 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 9387 hom., cov: 32)

Exomes 𝑓: 0.33 ( 82715 hom. )

Consequence

IFNB1
NM_002176.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.855

Variant links:

Genes affected

IFNB1 (HGNC:5434): (interferon beta 1) This gene encodes a cytokine that belongs to the interferon family of signaling proteins, which are released as part of the innate immune response to pathogens. The protein encoded by this gene belongs to the type I class of interferons, which are important for defense against viral infections. In addition, type I interferons are involved in cell differentiation and anti-tumor defenses. Following secretion in response to a pathogen, type I interferons bind a homologous receptor complex and induce transcription of genes such as those encoding inflammatory cytokines and chemokines. Overactivation of type I interferon secretion is linked to autoimmune diseases. Mice deficient for this gene display several phenotypes including defects in B cell maturation and increased susceptibility to viral infection. [provided by RefSeq, Sep 2015]

IFNB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP7

Synonymous conserved (PhyloP=-0.855 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNB1	NM_002176.4 link	c.153C>T	p.Tyr51Tyr	synonymous_variant	Exon 1 of 1	ENST00000380232.4	NP_002167.1	P01574A0A7R8GV38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNB1	ENST00000380232.4 link	c.153C>T	p.Tyr51Tyr	synonymous_variant	Exon 1 of 1	6	NM_002176.4	ENSP00000369581.2		P01574

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

52985

AN:

151880

Hom.:

9377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.304

GnomAD2 exomes

AF:

0.328

AC:

82157

AN:

250568

AF XY:

0.325

show subpopulations

Gnomad AFR exome

AF:

0.376

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.433

Gnomad NFE exome

AF:

0.342

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.334

AC:

488312

AN:

1461310

Hom.:

82715

Cov.:

AF XY:

0.332

AC XY:

241664

AN XY:

726978

show subpopulations

African (AFR)

AF:

0.381

AC:

12753

AN:

33442

American (AMR)

AF:

0.260

AC:

11615

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

8207

AN:

26126

East Asian (EAS)

AF:

0.395

AC:

15685

AN:

39684

South Asian (SAS)

AF:

0.257

AC:

22202

AN:

86244

European-Finnish (FIN)

AF:

0.431

AC:

22991

AN:

53390

Middle Eastern (MID)

AF:

0.304

AC:

1750

AN:

5766

European-Non Finnish (NFE)

AF:

0.336

AC:

373296

AN:

1111624

Other (OTH)

AF:

0.328

AC:

19813

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

18027

36054

54081

72108

90135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.349

AC:

53013

AN:

151998

Hom.:

9387

Cov.:

AF XY:

0.353

AC XY:

26186

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.376

AC:

15571

AN:

41456

American (AMR)

AF:

0.303

AC:

4616

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

1092

AN:

3470

East Asian (EAS)

AF:

0.338

AC:

1746

AN:

5168

South Asian (SAS)

AF:

0.271

AC:

1310

AN:

4828

European-Finnish (FIN)

AF:

0.433

AC:

4570

AN:

10552

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.341

AC:

23190

AN:

67960

Other (OTH)

AF:

0.304

AC:

643

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1758

3516

5273

7031

8789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.332

Hom.:

28862

Bravo

AF:

0.337

Asia WGS

AF:

0.298

AC:

1039

AN:

3478

EpiCase

AF:

0.332

EpiControl

AF:

0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.28

(source)

DANN

Benign

0.17

PhyloP100

-0.85

PromoterAI

0.010

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

LitVar

Below is the list of publications found by LitVar for variant 9:21077717 G>A . It may be empty.

rs1051922

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over