chr11-68046463-A-G

Position:

• chr11-68046463-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006019.4(TCIRG1):​c.1166-970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,152 control chromosomes in the GnomAD database, including 51,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.82 (51025 hom., cov: 31)
• Consequence: TCIRG1 NM_006019.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.886

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 11-68046463-A-G is Benign according to our data. Variant chr11-68046463-A-G is described in ClinVar as [Benign]. Clinvar id is 235422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCIRG1	NM_006019.4	c.1166-970A>G		intron_variant		ENST00000265686.8	NP_006010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCIRG1	ENST00000265686.8	c.1166-970A>G		intron_variant		1	NM_006019.4	ENSP00000265686	P1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124470 AN: 152034 Hom.: 50988 Cov.: 31

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.819 AC: 124560 AN: 152152 Hom.: 51025 Cov.: 31 AF XY: 0.818 AC XY: 60835 AN XY: 74356

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.838

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.851

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.832

Alfa AF: 0.827 Hom.: 11364

Bravo AF: 0.827

Asia WGS AF: 0.830 AC: 2888 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jan 22, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs906713; hg19: chr11-67813930;