rs76956521

Variant names:

• chr5-151085080-A-C
• rs76956521
• ENST00000315050.11:c.-37+2005T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-151085080-A-C
• chr5-151085080-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000315050.11(TNIP1):​c.-37+2005T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 152,252 control chromosomes in the GnomAD database, including 277 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 0.053 (277 hom., cov: 32)
• Consequence: TNIP1 ENST00000315050.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 13 publications found

Genes affected

TNIP1 (HGNC:16903): (TNFAIP3 interacting protein 1) This gene encodes an A20-binding protein which plays a role in autoimmunity and tissue homeostasis through the regulation of nuclear factor kappa-B activation. Mutations in this gene have been associated with psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

TNIP1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000315050.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIP1	NM_001252390.2		c.-37+2511T>G		intron	N/A	NP_001239319.1
	TNIP1	NM_001252391.2		c.-37+2005T>G		intron	N/A	NP_001239320.1
	TNIP1	NM_001437734.1		c.-33+2005T>G		intron	N/A	NP_001424663.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIP1	ENST00000315050.11	TSL:1	c.-37+2005T>G		intron	N/A	ENSP00000317891.7
	TNIP1	ENST00000523338.5	TSL:1	c.-37+2005T>G		intron	N/A	ENSP00000428243.1
	TNIP1	ENST00000521001.2	TSL:4	c.-37+8358T>G		intron	N/A	ENSP00000428404.2

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8136 AN: 152140 Hom.: 276 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.0656

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0534 AC: 8133 AN: 152252 Hom.: 277 Cov.: 32 AF XY: 0.0557 AC XY: 4148 AN XY: 74450

African (AFR) AF: 0.0231 AC: 960 AN: 41530

American (AMR) AF: 0.0398 AC: 609 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 304 AN: 3470

East Asian (EAS) AF: 0.111 AC: 575 AN: 5184

South Asian (SAS) AF: 0.143 AC: 692 AN: 4824

European-Finnish (FIN) AF: 0.0647 AC: 686 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0598 AC: 4070 AN: 68032

Other (OTH) AF: 0.0682 AC: 144 AN: 2112

Alfa AF: 0.0321 Hom.: 27

Bravo AF: 0.0481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.42
PhyloP100		-0.0090
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: rs76956521; hg19: chr5-150464641;