chr21-29506044-T-G

Variant names:

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

Variant summary

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

The ENST00000422809.5(BACH1):​c.472-76268T>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 ENST00000422809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.228 AC: 9475 AN: 41494

American (AMR) AF: 0.605 AC: 9238 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2517 AN: 3472

East Asian (EAS) AF: 0.601 AC: 3109 AN: 5170

South Asian (SAS) AF: 0.750 AC: 3605 AN: 4808

European-Finnish (FIN) AF: 0.820 AC: 8693 AN: 10600

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54612 AN: 67990

Other (OTH) AF: 0.637 AC: 1344 AN: 2110

Alfa AF: 0.745 Hom.: 73499

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
PhyloP100		-2.4

Splicing

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

Other links and lift over

dbSNP: rs2070398; hg19: chr21-30878364;