rs6454792

Positions:

• chr6-89977354-G-A

Variant summary

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

The NM_021813.4(BACH2):​c.244-25492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,080 control chromosomes in the GnomAD database, including 22,741 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 0.54 (22741 hom., cov: 33)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

Genes affected

BACH2 (HGNC:14078): (BTB domain and CNC homolog 2) Enables sequence-specific double-stranded DNA binding activity. Involved in primary adaptive immune response involving T cells and B cells. Located in cytosol and nucleoplasm. Implicated in immunodeficiency 60. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BACH2	NM_021813.4	c.244-25492C>T		intron_variant		ENST00000257749.9
BACH2	NM_001170794.2	c.244-25492C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BACH2	ENST00000257749.9	c.244-25492C>T		intron_variant		1	NM_021813.4	P1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82627 AN: 151960 Hom.: 22704 Cov.: 33

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.544 AC: 82716 AN: 152080 Hom.: 22741 Cov.: 33 AF XY: 0.539 AC XY: 40079 AN XY: 74352

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.551

Alfa AF: 0.534 Hom.: 28950

Bravo AF: 0.546

Asia WGS AF: 0.396 AC: 1373 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.61

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: rs6454792; hg19: chr6-90687073; COSMIC: COSV57605619;