6-90286630-C-T

Variant names:

• chr6-90286630-C-T
• rs4142967
• NM_021813.4:c.-446+9850G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021813.4(BACH2):​c.-446+9850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,002 control chromosomes in the GnomAD database, including 11,708 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 0.38 (11708 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 17 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 -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 = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-446+9850G>A		intron_variant	Intron 1 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-275+9850G>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.-446+9850G>A		intron_variant	Intron 1 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57710 AN: 151884 Hom.: 11687 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.380 AC: 57758 AN: 152002 Hom.: 11708 Cov.: 32 AF XY: 0.371 AC XY: 27596 AN XY: 74300

African (AFR) AF: 0.302 AC: 12489 AN: 41420

American (AMR) AF: 0.374 AC: 5709 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1376 AN: 3472

East Asian (EAS) AF: 0.0488 AC: 253 AN: 5180

South Asian (SAS) AF: 0.405 AC: 1955 AN: 4822

European-Finnish (FIN) AF: 0.331 AC: 3501 AN: 10562

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31038 AN: 67960

Other (OTH) AF: 0.385 AC: 809 AN: 2102

Alfa AF: 0.420 Hom.: 7772

Bravo AF: 0.378

Asia WGS AF: 0.232 AC: 809 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	0.50
DANN	Benign	0.29
PhyloP100		-0.30
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: rs4142967; hg19: chr6-90996349; COSMIC: COSV57606721;