rs1124769

Positions:

• chr15-51060052-A-G
• chr15-51060052-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001311175.2(TNFAIP8L3):​c.53-1609T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,268 control chromosomes in the GnomAD database, including 2,895 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 0.17 (2895 hom., cov: 33)
• Consequence: TNFAIP8L3 NM_001311175.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

Genes affected

TNFAIP8L3 (HGNC:20620): (TNF alpha induced protein 8 like 3) Predicted to enable phosphatidylinositol binding activity and phosphatidylinositol transfer activity. Predicted to be involved in several processes, including inositol lipid-mediated signaling; positive regulation of intracellular signal transduction; and positive regulation of phosphatidylinositol 3-kinase activity. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MIR4713HG (HGNC:53124): (MIR4713 host gene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP8L3	NM_001311175.2	c.53-1609T>C		intron_variant		ENST00000637513.2	NP_001298104.1
MIR4713HG	NR_146310.1	n.194+22371A>G		intron_variant, non_coding_transcript_variant
TNFAIP8L3	NM_207381.4	c.317-1609T>C		intron_variant			NP_997264.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP8L3	ENST00000637513.2	c.53-1609T>C		intron_variant		1	NM_001311175.2	ENSP00000489743	P1
TNFAIP8L3	ENST00000327536.5	c.317-1609T>C		intron_variant		1		ENSP00000328016
MIR4713HG	ENST00000559909.1	n.194+22371A>G		intron_variant, non_coding_transcript_variant		4
TNFAIP8L3	ENST00000649177.1	c.-86-1609T>C		intron_variant				ENSP00000498365

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25804 AN: 152150 Hom.: 2894 Cov.: 33

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.169 AC: 25804 AN: 152268 Hom.: 2895 Cov.: 33 AF XY: 0.172 AC XY: 12824 AN XY: 74452

Gnomad4 AFR AF: 0.0409

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.170

Alfa AF: 0.184 Hom.: 1807

Bravo AF: 0.162

Asia WGS AF: 0.239 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.66

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: rs1124769; hg19: chr15-51352249;