rs13173226

Positions:

• chr5-135450569-T-C

Variant summary

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

The NM_001099221.2(TIFAB):​c.-10-620A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,178 control chromosomes in the GnomAD database, including 5,371 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 0.25 (5369 hom., cov: 32)
  • Exomes 𝑓: 0.27 (2 hom.)
• Consequence: TIFAB NM_001099221.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

TIFAB (HGNC:34024): (TIFA inhibitor) Involved in several processes, including animal organ morphogenesis; cranial nerve development; and hard palate morphogenesis. [provided by Alliance of Genome Resources, Apr 2022]

LOC124901073 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIFAB	NM_001099221.2	c.-10-620A>G		intron_variant		ENST00000537858.2	NP_001092691.1
LOC124901073	XR_007058945.1	n.70T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIFAB	ENST00000537858.2	c.-10-620A>G		intron_variant		1	NM_001099221.2	ENSP00000440509	P1
	ENST00000510230.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38735 AN: 151986 Hom.: 5356 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.270 AC: 20 AN: 74 Hom.: 2 Cov.: 0 AF XY: 0.333 AC XY: 14 AN XY: 42

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.255 AC: 38770 AN: 152104 Hom.: 5369 Cov.: 32 AF XY: 0.252 AC XY: 18720 AN XY: 74350

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.296

Alfa AF: 0.301 Hom.: 10053

Bravo AF: 0.264

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.86
DANN	Benign	0.82

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: rs13173226; hg19: chr5-134786259;