rs210134

Variant names:

• chr6-33572432-A-G
• rs210134
• ENST00000612409.1:n.248+1621A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-33572432-A-G
• chr6-33572432-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000612409.1(GGNBP1):​n.248+1621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 152,730 control chromosomes in the GnomAD database, including 39,825 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 0.72 (39648 hom., cov: 31)
  • Exomes 𝑓: 0.73 (177 hom.)
• Consequence: GGNBP1 ENST00000612409.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774

Genes affected

GGNBP1 (HGNC:19427): (gametogenetin binding protein 1 (pseudogene)) This gene is the ortholog of the mouse gametogenetin-binding protein 1 gene. In human, the open reading frame is disrupted by a nonsense mutation after 8-aa; consequently, this gene is currently considered to be a unitary pseudogene in human even though it is functional in other mammals. [provided by RefSeq, Aug 2009]

BAK1 (HGNC:949): (BCL2 antagonist/killer 1) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAK1	NM_001188.4	c.*1371T>C		downstream_gene_variant		ENST00000374467.4	NP_001179.1
BAK1	XM_011514779.4	c.*1371T>C		downstream_gene_variant			XP_011513081.1
BAK1	XM_011514780.2	c.*1371T>C		downstream_gene_variant			XP_011513082.1
BAK1	XM_047419196.1	c.*1371T>C		downstream_gene_variant			XP_047275152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGNBP1	ENST00000612409.1	n.248+1621A>G		intron_variant	Intron 3 of 5	5
BAK1	ENST00000374467.4	c.*1371T>C		downstream_gene_variant		1	NM_001188.4	ENSP00000363591.3
BAK1	ENST00000442998.6	c.*1565T>C		downstream_gene_variant		1		ENSP00000391258.2

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109613 AN: 151956 Hom.: 39610 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.707

GnomAD4 exome AF: 0.732 AC: 480 AN: 656 Hom.: 177 AF XY: 0.760 AC XY: 254 AN XY: 334

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.758

Gnomad4 FIN exome AF: 0.726

Gnomad4 NFE exome AF: 0.727

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.721 AC: 109704 AN: 152074 Hom.: 39648 Cov.: 31 AF XY: 0.725 AC XY: 53906 AN XY: 74344

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.703

Alfa AF: 0.708 Hom.: 77772

Bravo AF: 0.715

Asia WGS AF: 0.701 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs210134; hg19: chr6-33540209;