rs2229231

Variant names:

• chr9-21077642-G-A
• rs2229231
• NM_002176.4:c.228C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-21077642-G-A
• chr9-21077642-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002176.4(IFNB1):​c.228C>T​(p.Ala76Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,613,904 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (14 hom.)
• Consequence: IFNB1 NM_002176.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.28
• Publications: 6 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-21077642-G-A is Benign according to our data. Variant chr9-21077642-G-A is described in ClinVar as Benign. ClinVar VariationId is 717236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.28 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00733 (1116/152250) while in subpopulation AFR AF = 0.0258 (1072/41560). AF 95% confidence interval is 0.0245. There are 11 homozygotes in GnomAd4. There are 533 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002176.4. 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
	IFNB1	NM_002176.4	MANE Select	c.228C>T	p.Ala76Ala	synonymous	Exon 1 of 1	NP_002167.1	P01574

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNB1	ENST00000380232.4	TSL:6 MANE Select	c.228C>T	p.Ala76Ala	synonymous	Exon 1 of 1	ENSP00000369581.2	P01574

Frequencies

GnomAD3 genomes AF: 0.00731 AC: 1112 AN: 152132 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00180 AC: 451 AN: 250678 AF XY: 0.00138

Gnomad AFR exome AF: 0.0258

Gnomad AMR exome AF: 0.000753

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000746 AC: 1090 AN: 1461654 Hom.: 14 Cov.: 32 AF XY: 0.000624 AC XY: 454 AN XY: 727128

African (AFR) AF: 0.0277 AC: 927 AN: 33458

American (AMR) AF: 0.00112 AC: 50 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111866

Other (OTH) AF: 0.00129 AC: 78 AN: 60388

GnomAD4 genome AF: 0.00733 AC: 1116 AN: 152250 Hom.: 11 Cov.: 32 AF XY: 0.00716 AC XY: 533 AN XY: 74416

African (AFR) AF: 0.0258 AC: 1072 AN: 41560

American (AMR) AF: 0.00196 AC: 30 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68014

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00128 Hom.: 1

Bravo AF: 0.00807

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.28
PhyloP100		-2.3
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	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: rs2229231; hg19: chr9-21077641;