chr6-90248512-C-G

Position:

• chr6-90248512-C-G

Variant summary

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

The NM_021813.4(BACH2):​c.-275+4001G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,926 control chromosomes in the GnomAD database, including 11,074 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 0.37 (11074 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-275+4001G>C		intron_variant		ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-274-41831G>C		intron_variant			NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.-275+4001G>C		intron_variant		1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56074 AN: 151808 Hom.: 11060 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.369 AC: 56107 AN: 151926 Hom.: 11074 Cov.: 32 AF XY: 0.366 AC XY: 27156 AN XY: 74206

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.405

Alfa AF: 0.431 Hom.: 7912

Bravo AF: 0.368

Asia WGS AF: 0.378 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.73

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: rs11755527; hg19: chr6-90958231;