dbSNP rs147119415: TBC1D24:c.-115-140C>A (chr16-2495894-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001199107.2(TBC1D24):c.-115-140C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 477,630 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 2 hom. )

Consequence

TBC1D24
NM_001199107.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.292

Variant links:

Genes affected

TBC1D24 (HGNC:29203): (TBC1 domain family member 24) This gene encodes a protein with a conserved domain, referred to as the TBC domain, characteristic of proteins which interact with GTPases. TBC domain proteins may serve as GTPase-activating proteins for a particular group of GTPases, the Rab (Ras-related proteins in brain) small GTPases which are involved in the regulation of membrane trafficking. Mutations in this gene are associated with familial infantile myoclonic epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]

TBC1D24 links:

ENSG00000260272 (HGNC:):

ENSG00000260272 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 16-2495894-C-A is Benign according to our data. Variant chr16-2495894-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1207448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00632 (961/151938) while in subpopulation AFR AF = 0.0171 (708/41456). AF 95% confidence interval is 0.016. There are 7 homozygotes in GnomAd4. There are 444 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D24	NM_001199107.2 link	c.-115-140C>A		intron_variant	Intron 1 of 7	ENST00000646147.1	NP_001186036.1	Q9ULP9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D24	ENST00000646147.1 link	c.-115-140C>A		intron_variant	Intron 1 of 7		NM_001199107.2	ENSP00000494678.1		Q9ULP9-1
ENSG00000260272	ENST00000564543.1 link	c.-255C>A		upstream_gene_variant		2		ENSP00000455547.1		H3BQ06

Frequencies

GnomAD3 genomes

AF:

0.00629

AC:

955

AN:

151820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00853

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0224

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00576

GnomAD4 exome

AF:

0.00191

AC:

622

AN:

325692

Hom.:

AF XY:

0.00181

AC XY:

310

AN XY:

171676

show subpopulations

African (AFR)

AF:

0.0190

AC:

183

AN:

9628

American (AMR)

AF:

0.00675

AC:

AN:

14080

Ashkenazi Jewish (ASJ)

AF:

0.00684

AC:

AN:

9942

East Asian (EAS)

AF:

0.00

AC:

AN:

19644

South Asian (SAS)

AF:

0.0000728

AC:

AN:

41192

European-Finnish (FIN)

AF:

0.0000619

AC:

AN:

16160

Middle Eastern (MID)

AF:

0.00492

AC:

AN:

1422

European-Non Finnish (NFE)

AF:

0.000973

AC:

190

AN:

195236

Other (OTH)

AF:

0.00408

AC:

AN:

18388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00632

AC:

961

AN:

151938

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

444

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.0171

AC:

708

AN:

41456

American (AMR)

AF:

0.00851

AC:

130

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0241

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00115

AC:

AN:

67928

Other (OTH)

AF:

0.00570

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

138

184

230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00585

Hom.:

Bravo

AF:

0.00731

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 22, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.2

(source)

DANN

Benign

0.60

PhyloP100

0.29

PromoterAI

0.0023

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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rs147119415

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over