rs2289577

Positions:

• chr6-89930772-C-T

Variant summary

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

The NM_021813.4(BACH2):​c.*1636G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,522 control chromosomes in the GnomAD database, including 973 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 0.11 (971 hom., cov: 32)
  • Exomes 𝑓: 0.076 (2 hom.)
• Consequence: BACH2 NM_021813.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACH2	NM_021813.4	c.*1636G>A		3_prime_UTR_variant	9/9	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.*1636G>A		3_prime_UTR_variant	7/7		NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749	c.*1636G>A		3_prime_UTR_variant	9/9	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16124 AN: 152114 Hom.: 965 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.0698

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.0759 AC: 22 AN: 290 Hom.: 2 Cov.: 0 AF XY: 0.0604 AC XY: 11 AN XY: 182

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.0833

Gnomad4 FIN exome AF: 0.0806

Gnomad4 NFE exome AF: 0.0455

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.106 AC: 16160 AN: 152232 Hom.: 971 Cov.: 32 AF XY: 0.104 AC XY: 7749 AN XY: 74440

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.0696

Gnomad4 SAS AF: 0.0313

Gnomad4 FIN AF: 0.0835

Gnomad4 NFE AF: 0.0944

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0937 Hom.: 984

Bravo AF: 0.109

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.2
DANN	Benign	0.84

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: rs2289577; hg19: chr6-90640491;