rs3808974

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006019.4(TCIRG1):c.417+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,549,548 control chromosomes in the GnomAD database, including 58,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8480 hom., cov: 34)

Exomes 𝑓: 0.26 ( 50216 hom. )

Consequence

TCIRG1
NM_006019.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.153

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive osteopetrosis
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Myriad Women’s Health, Orphanet
autosomal recessive osteopetrosis 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia
autosomal dominant severe congenital neutropenia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive osteopetrosis 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
dysosteosclerosis
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet

TCIRG1 links:

Genome browser will be placed here

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=-0.89).

BP6

Variant 11-68042874-A-G is Benign according to our data. Variant chr11-68042874-A-G is described in ClinVar as Benign. ClinVar VariationId is 197264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006019.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TCIRG1	NM_006019.4	MANE Select	c.417+11A>G	intron	N/A	NP_006010.2
TCIRG1	NM_001440552.1		c.417+11A>G	intron	N/A	NP_001427481.1
TCIRG1	NM_001440553.1		c.417+11A>G	intron	N/A	NP_001427482.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TCIRG1	ENST00000265686.8	TSL:1 MANE Select	c.417+11A>G	intron	N/A	ENSP00000265686.3	Q13488-1
TCIRG1	ENST00000698255.1		c.417+11A>G	intron	N/A	ENSP00000513630.1	A0A8V8TM28
TCIRG1	ENST00000698254.1		c.403+25A>G	intron	N/A	ENSP00000513629.1	A0A8V8TN16

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48334

AN:

151868

Hom.:

8466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.289

GnomAD2 exomes

AF:

0.245

AC:

36770

AN:

149916

AF XY:

0.241

show subpopulations

Gnomad AFR exome

AF:

0.489

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.264

AC:

369545

AN:

1397562

Hom.:

50216

Cov.:

AF XY:

0.262

AC XY:

180646

AN XY:

689270

show subpopulations

African (AFR)

AF:

0.485

AC:

15310

AN:

31578

American (AMR)

AF:

0.203

AC:

7233

AN:

35676

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

6142

AN:

25156

East Asian (EAS)

AF:

0.263

AC:

9380

AN:

35732

South Asian (SAS)

AF:

0.180

AC:

14272

AN:

79236

European-Finnish (FIN)

AF:

0.224

AC:

10743

AN:

48052

Middle Eastern (MID)

AF:

0.253

AC:

1409

AN:

5568

European-Non Finnish (NFE)

AF:

0.269

AC:

289773

AN:

1078648

Other (OTH)

AF:

0.264

AC:

15283

AN:

57916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

17345

34691

52036

69382

86727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9822

19644

29466

39288

49110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.318

AC:

48396

AN:

151986

Hom.:

8480

Cov.:

AF XY:

0.314

AC XY:

23294

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.476

AC:

19736

AN:

41480

American (AMR)

AF:

0.249

AC:

3816

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

802

AN:

3472

East Asian (EAS)

AF:

0.245

AC:

1255

AN:

5114

South Asian (SAS)

AF:

0.175

AC:

844

AN:

4828

European-Finnish (FIN)

AF:

0.216

AC:

2285

AN:

10568

Middle Eastern (MID)

AF:

0.195

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.275

AC:

18687

AN:

67910

Other (OTH)

AF:

0.286

AC:

604

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1647

3293

4940

6586

8233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.286

Hom.:

1418

Bravo

AF:

0.325

Asia WGS

AF:

0.233

AC:

812

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive osteopetrosis 1 (2)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.4

(source)

DANN

Benign

0.64

PhyloP100

-0.15

PromoterAI

-0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over