rs1847472

Positions:

• chr6-90263440-C-A

Variant summary

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

The NM_021813.4(BACH2):​c.-353+8409G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,086 control chromosomes in the GnomAD database, including 5,695 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 0.25 (5695 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BACH2	NM_021813.4	c.-353+8409G>T		intron_variant		ENST00000257749.9
BACH2	NM_001170794.2	c.-275+33040G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BACH2	ENST00000257749.9	c.-353+8409G>T		intron_variant		1	NM_021813.4	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38577 AN: 151968 Hom.: 5688 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0450

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.254 AC: 38599 AN: 152086 Hom.: 5695 Cov.: 32 AF XY: 0.248 AC XY: 18472 AN XY: 74366

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.0453

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.272

Alfa AF: 0.327 Hom.: 17483

Bravo AF: 0.250

Asia WGS AF: 0.157 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.44

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: rs1847472; hg19: chr6-90973159;