rs4572866

Variant names:

• chr4-26793981-T-C
• rs4572866
• XR_001741277.2:n.1833-19700T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_001741277.2(TBC1D19):​n.1833-19700T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,098 control chromosomes in the GnomAD database, including 5,830 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 (5830 hom., cov: 32)
• Consequence: TBC1D19 XR_001741277.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 6 publications found

Genes affected

TBC1D19 (HGNC:25624): (TBC1 domain family member 19) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

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 (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D19	XR_001741277.2	n.1833-19700T>C		intron_variant	Intron 22 of 22
TBC1D19	XR_007057937.1	n.1713+29244T>C		intron_variant	Intron 20 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38015 AN: 151980 Hom.: 5830 Cov.: 32

Gnomad AFR AF: 0.0799

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.250 AC: 38001 AN: 152098 Hom.: 5830 Cov.: 32 AF XY: 0.245 AC XY: 18240 AN XY: 74346

African (AFR) AF: 0.0796 AC: 3304 AN: 41532

American (AMR) AF: 0.268 AC: 4091 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1159 AN: 3466

East Asian (EAS) AF: 0.0893 AC: 463 AN: 5184

South Asian (SAS) AF: 0.338 AC: 1629 AN: 4822

European-Finnish (FIN) AF: 0.265 AC: 2797 AN: 10546

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23468 AN: 67954

Other (OTH) AF: 0.267 AC: 564 AN: 2110

Alfa AF: 0.314 Hom.: 6645

Bravo AF: 0.245

Asia WGS AF: 0.210 AC: 731 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	3.5
DANN	Benign	0.76
PhyloP100		0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4572866; hg19: chr4-26795603;