rs210135

Positions:

• chr6-33572915-T-A
• chr6-33572915-T-C
• chr6-33572915-T-G

Variant summary

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

The NM_001188.4(BAK1):​c.*888A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 148,766 control chromosomes in the GnomAD database, including 40,449 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 0.74 (40404 hom., cov: 24)
  • Exomes 𝑓: 0.48 (45 hom.)
• Consequence: BAK1 NM_001188.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAK1	NM_001188.4	c.*888A>T		3_prime_UTR_variant	6/6	ENST00000374467.4	NP_001179.1
BAK1	XM_011514779.4	c.*888A>T		3_prime_UTR_variant	7/7		XP_011513081.1
BAK1	XM_011514780.2	c.*888A>T		3_prime_UTR_variant	5/5		XP_011513082.1
BAK1	XM_047419196.1	c.*888A>T		3_prime_UTR_variant	5/5		XP_047275152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAK1	ENST00000374467.4	c.*888A>T		3_prime_UTR_variant	6/6	1	NM_001188.4	ENSP00000363591	P1
BAK1	ENST00000442998.6	c.*1082A>T		3_prime_UTR_variant	7/7	1		ENSP00000391258
GGNBP1	ENST00000612409.1	n.248+2104T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.736 AC: 109248 AN: 148440 Hom.: 40345 Cov.: 24

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.721

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.476 AC: 99 AN: 208 Hom.: 45 Cov.: 0 AF XY: 0.453 AC XY: 48 AN XY: 106

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.0500

Gnomad4 FIN exome AF: 0.601

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.736 AC: 109363 AN: 148558 Hom.: 40404 Cov.: 24 AF XY: 0.741 AC XY: 53590 AN XY: 72322

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.731

Alfa AF: 0.725 Hom.: 4598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs210135; hg19: chr6-33540692;