rs5997096

chr22-26499991-T-C

Variant summary

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

The NM_012143.4(TFIP11):c.802-360A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,982 control chromosomes in the GnomAD database, including 17,237 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 0.47 (17237 hom., cov: 32)
• Consequence: TFIP11 NM_012143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

Genes affected

TFIP11 (HGNC:17165): (tuftelin interacting protein 11) This gene encodes a protein component of the spliceosome that promotes the release of the lariat-intron during late-stage splicing through the recruitment of a pre-mRNA splicing factor called DEAH-box helicase 15. The encoded protein contains a G-patch domain, a hallmark of RNA-processing proteins, that binds DEAH-box helicase 15. This protein contains an atypical nuclear localization sequence as well as a nuclear speckle-targeting sequence, enabling it to localize to distinct speckled regions within the cell nucleus. Polymorphisms in this gene are associated with dental caries suggesting a role in amelogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFIP11	NM_012143.4	c.802-360A>G		intron_variant		ENST00000407690.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFIP11	ENST00000407690.6	c.802-360A>G		intron_variant		1	NM_012143.4	P1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71053 AN: 151864 Hom.: 17237 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.468 AC: 71064 AN: 151982 Hom.: 17237 Cov.: 32 AF XY: 0.472 AC XY: 35039 AN XY: 74270

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.484

Alfa AF: 0.495 Hom.: 2412

Bravo AF: 0.449

Asia WGS AF: 0.439 AC: 1529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.28
Dann	Benign	0.71

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: rs5997096; hg19: chr22-26895957;