rs76956521

chr5-151085080-A-Cchr5-151085080-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNIP1	NM_001252390.2	c.-37+2511T>G		intron_variant
TNIP1	NM_001252391.2	c.-37+2005T>G		intron_variant
TNIP1	NM_001252392.2	c.-37+2005T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNIP1	ENST00000315050.11	c.-37+2005T>G		intron_variant		1		P3
TNIP1	ENST00000523338.5	c.-37+2005T>G		intron_variant		1
TNIP1	ENST00000521001.1	c.-37+8358T>G		intron_variant		4

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

Gnomad4 AFR AF: 0.0231

Gnomad4 AMR AF: 0.0398

Gnomad4 ASJ AF: 0.0876

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.0598

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0295 Hom.: 23

Bravo AF: 0.0481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.7
Dann	Benign	0.42

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

Other links and lift over

dbSNP: rs76956521; hg19: chr5-150464641;