21-29506044-T-G

Variant names:

• chr21-29506044-T-G
• rs2070398
• ENST00000422809.5:c.472-76268T>G

Variant summary

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

The ENST00000468059.1(BACH1):​c.325-91526T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,128 control chromosomes in the GnomAD database, including 33,516 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 0.62 (33516 hom., cov: 32)
• Consequence: BACH1 ENST00000468059.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

Genes affected

BACH1 (HGNC:935): (BTB domain and CNC homolog 1) This gene encodes a transcription factor that belongs to the cap'n'collar type of basic region leucine zipper factor family (CNC-bZip). The encoded protein contains broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domains, which is atypical of CNC-bZip family members. These BTB/POZ domains facilitate protein-protein interactions and formation of homo- and/or hetero-oligomers. When this encoded protein forms a heterodimer with MafK, it functions as a repressor of Maf recognition element (MARE) and transcription is repressed. Multiple alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2009]

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 (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000422809.5	c.472-76268T>G		intron_variant	Intron 2 of 4	5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.325-91526T>G		intron_variant	Intron 2 of 3	3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93574 AN: 152010 Hom.: 33509 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.615 AC: 93586 AN: 152128 Hom.: 33516 Cov.: 32 AF XY: 0.618 AC XY: 45967 AN XY: 74378

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.637

Alfa AF: 0.764 Hom.: 60379

Bravo AF: 0.580

Asia WGS AF: 0.617 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2070398; hg19: chr21-30878364;