rs6454792

Variant names:

• chr6-89977354-G-A
• rs6454792
• NM_021813.4:c.244-25492C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

BACH2 Gene-Disease associations (from GenCC):

• immunodeficiency 60

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.244-25492C>T		intron_variant	Intron 6 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.244-25492C>T		intron_variant	Intron 4 of 6		NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.244-25492C>T		intron_variant	Intron 6 of 8	1	NM_021813.4	ENSP00000257749.4

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

African (AFR) AF: 0.602 AC: 24973 AN: 41464

American (AMR) AF: 0.545 AC: 8329 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1761 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1733 AN: 5174

South Asian (SAS) AF: 0.421 AC: 2035 AN: 4828

European-Finnish (FIN) AF: 0.521 AC: 5496 AN: 10552

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36577 AN: 67980

Other (OTH) AF: 0.551 AC: 1164 AN: 2112

Alfa AF: 0.535 Hom.: 34366

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
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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