dbSNP rs2075609: TCIRG1:c.1887+175A>G (chr11-68049469-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006019.4(TCIRG1):c.1887+175A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 980,062 control chromosomes in the GnomAD database, including 39,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8005 hom., cov: 33)

Exomes 𝑓: 0.27 ( 31348 hom. )

Consequence

TCIRG1
NM_006019.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.375

Variant links:

Genes affected

TCIRG1 (HGNC:11647): (T cell immune regulator 1, ATPase H+ transporting V0 subunit a3) This gene encodes a subunit of a large protein complex known as a vacuolar H+-ATPase (V-ATPase). The protein complex acts as a pump to move protons across the membrane. This movement of protons helps regulate the pH of cells and their surrounding environment. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. V-ATPase is comprised of a cytosolic V1 domain and a transmembrane V0 domain. Alternative splicing results in multiple transcript variants. Mutations in this gene are associated with infantile malignant osteopetrosis. [provided by RefSeq, May 2017]

TCIRG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-68049469-A-G is Benign according to our data. Variant chr11-68049469-A-G is described in ClinVar as [Benign]. Clinvar id is 1276806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCIRG1	NM_006019.4 link	c.1887+175A>G		intron_variant	Intron 15 of 19	ENST00000265686.8	NP_006010.2	Q13488-1A0A024R5E5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCIRG1	ENST00000265686.8 link	c.1887+175A>G		intron_variant	Intron 15 of 19	1	NM_006019.4	ENSP00000265686.3		Q13488-1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47804

AN:

152022

Hom.:

7992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.293

GnomAD4 exome

AF:

0.270

AC:

223331

AN:

827922

Hom.:

31348

Cov.:

AF XY:

0.269

AC XY:

112643

AN XY:

418710

show subpopulations

Gnomad4 AFR exome

AF:

0.441

Gnomad4 AMR exome

AF:

0.194

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.218

Gnomad4 NFE exome

AF:

0.270

Gnomad4 OTH exome

AF:

0.275

GnomAD4 genome

AF:

0.315

AC:

47859

AN:

152140

Hom.:

8005

Cov.:

AF XY:

0.309

AC XY:

23002

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.441

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.291

Alfa

AF:

0.262

Hom.:

4366

Bravo

AF:

0.320

Asia WGS

AF:

0.303

AC:

1055

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive osteopetrosis 1

Benign:1

Aug 29, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.68

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over