rs370409

Positions:

• chr6-90212021-C-A
• chr6-90212021-C-G
• chr6-90212021-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.-274-5340G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,046 control chromosomes in the GnomAD database, including 45,011 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 0.76 (45011 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-274-5340G>T		intron_variant		ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-274-5340G>T		intron_variant			NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.-274-5340G>T		intron_variant		1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115169 AN: 151928 Hom.: 44944 Cov.: 32

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.758 AC: 115299 AN: 152046 Hom.: 45011 Cov.: 32 AF XY: 0.755 AC XY: 56069 AN XY: 74286

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.780

Alfa AF: 0.699 Hom.: 78214

Bravo AF: 0.782

Asia WGS AF: 0.731 AC: 2544 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.60

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: rs370409; hg19: chr6-90921740;