rs260960

Variant names:

• chr4-26631362-C-T
• rs260960
• NM_018317.4:c.295-5849C>T

Variant summary

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

The NM_018317.4(TBC1D19):​c.295-5849C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,832 control chromosomes in the GnomAD database, including 11,781 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 0.38 (11781 hom., cov: 32)
• Consequence: TBC1D19 NM_018317.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D19	NM_018317.4	c.295-5849C>T		intron_variant	Intron 4 of 20	ENST00000264866.9	NP_060787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D19	ENST00000264866.9	c.295-5849C>T		intron_variant	Intron 4 of 20	1	NM_018317.4	ENSP00000264866.4

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57195 AN: 151714 Hom.: 11775 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.377 AC: 57196 AN: 151832 Hom.: 11781 Cov.: 32 AF XY: 0.376 AC XY: 27869 AN XY: 74180

African (AFR) AF: 0.214 AC: 8880 AN: 41446

American (AMR) AF: 0.339 AC: 5157 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1621 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1816 AN: 5174

South Asian (SAS) AF: 0.432 AC: 2081 AN: 4818

European-Finnish (FIN) AF: 0.422 AC: 4453 AN: 10544

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31697 AN: 67876

Other (OTH) AF: 0.398 AC: 837 AN: 2104

Alfa AF: 0.430 Hom.: 2963

Bravo AF: 0.364

Asia WGS AF: 0.373 AC: 1296 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.41
PhyloP100		1.6
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: rs260960; hg19: chr4-26632984;