rs2021716

Variant names:

• chr6-90231570-C-T
• rs2021716
• NM_021813.4:c.-275+20943G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_021813.4(BACH2):​c.-275+20943G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,146 control chromosomes in the GnomAD database, including 5,218 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 0.24 (5218 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.45
• Publications: 14 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-275+20943G>A		intron_variant	Intron 3 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-274-24889G>A		intron_variant	Intron 1 of 6		NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.-275+20943G>A		intron_variant	Intron 3 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35788 AN: 152026 Hom.: 5214 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.235 AC: 35789 AN: 152146 Hom.: 5218 Cov.: 32 AF XY: 0.230 AC XY: 17078 AN XY: 74382

African (AFR) AF: 0.0832 AC: 3454 AN: 41532

American (AMR) AF: 0.262 AC: 4005 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3468

East Asian (EAS) AF: 0.0235 AC: 122 AN: 5182

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4818

European-Finnish (FIN) AF: 0.233 AC: 2470 AN: 10582

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22487 AN: 67962

Other (OTH) AF: 0.253 AC: 534 AN: 2112

Alfa AF: 0.290 Hom.: 2643

Bravo AF: 0.230

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Benign	0.79
PhyloP100		3.5
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: rs2021716; hg19: chr6-90941289; COSMIC: COSV57606544;