6-89973325-C-T

Variant names:

• chr6-89973325-C-T
• rs11969265
• NM_021813.4:c.244-21463G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021813.4(BACH2):​c.244-21463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,102 control chromosomes in the GnomAD database, including 20,876 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 0.52 (20876 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.244-21463G>A		intron_variant	Intron 6 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.244-21463G>A		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.244-21463G>A		intron_variant	Intron 6 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79394 AN: 151984 Hom.: 20850 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.522 AC: 79452 AN: 152102 Hom.: 20876 Cov.: 32 AF XY: 0.522 AC XY: 38827 AN XY: 74366

African (AFR) AF: 0.508 AC: 21073 AN: 41478

American (AMR) AF: 0.523 AC: 7993 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1795 AN: 3466

East Asian (EAS) AF: 0.393 AC: 2032 AN: 5170

South Asian (SAS) AF: 0.469 AC: 2266 AN: 4828

European-Finnish (FIN) AF: 0.563 AC: 5948 AN: 10570

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36532 AN: 67976

Other (OTH) AF: 0.532 AC: 1126 AN: 2116

Alfa AF: 0.522 Hom.: 38477

Bravo AF: 0.515

Asia WGS AF: 0.448 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0020
DANN	Benign	0.46
PhyloP100		-1.6
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: rs11969265; hg19: chr6-90683044;