rs9344996

Variant names:

• chr6-90219582-T-C
• rs9344996
• NM_021813.4:c.-274-12901A>G

Variant summary

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

The NM_021813.4(BACH2):​c.-274-12901A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 152,264 control chromosomes in the GnomAD database, including 1,088 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 0.099 (1088 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• Publications: 6 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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-274-12901A>G		intron_variant	Intron 3 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-274-12901A>G		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.-274-12901A>G		intron_variant	Intron 3 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15064 AN: 152146 Hom.: 1086 Cov.: 32

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0971

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.0989 AC: 15059 AN: 152264 Hom.: 1088 Cov.: 32 AF XY: 0.102 AC XY: 7594 AN XY: 74438

African (AFR) AF: 0.0325 AC: 1353 AN: 41572

American (AMR) AF: 0.119 AC: 1815 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1847 AN: 5170

South Asian (SAS) AF: 0.160 AC: 770 AN: 4814

European-Finnish (FIN) AF: 0.0971 AC: 1028 AN: 10592

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7519 AN: 68030

Other (OTH) AF: 0.121 AC: 256 AN: 2112

Alfa AF: 0.108 Hom.: 1313

Bravo AF: 0.0991

Asia WGS AF: 0.214 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.59
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9344996; hg19: chr6-90929301; COSMIC: COSV57608255; COSMIC: COSV57608255;