rs13173226

Variant names:

• chr5-135450569-T-C
• rs13173226
• NM_001099221.2:c.-10-620A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TIFAB	NM_001099221.2	c.-10-620A>G		intron_variant	Intron 1 of 1	ENST00000537858.2	NP_001092691.1
LOC124901073	XR_007058945.1	n.70T>C		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIFAB	ENST00000537858.2	c.-10-620A>G		intron_variant	Intron 1 of 1	1	NM_001099221.2	ENSP00000440509.1
ENSG00000249639	ENST00000732724.1	n.255+1048T>C		intron_variant	Intron 2 of 2
ENSG00000249639	ENST00000510230.2	n.-18T>C		upstream_gene_variant		3
ENSG00000249639	ENST00000732725.1	n.-22T>C		upstream_gene_variant

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.308 AC: 16 AN: 52

Other (OTH) AF: 0.250 AC: 2 AN: 8

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

African (AFR) AF: 0.154 AC: 6406 AN: 41502

American (AMR) AF: 0.353 AC: 5398 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1245 AN: 5152

South Asian (SAS) AF: 0.227 AC: 1095 AN: 4820

European-Finnish (FIN) AF: 0.205 AC: 2175 AN: 10588

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20479 AN: 67982

Other (OTH) AF: 0.296 AC: 625 AN: 2110

Alfa AF: 0.298 Hom.: 13675

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
PhyloP100		-1.1
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: rs13173226; hg19: chr5-134786259;