21-29492828-T-C

Variant names:

• chr21-29492828-T-C
• rs2211887
• ENST00000422809.5:c.472-89484T>C

Variant summary

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

The ENST00000422809.5(BACH1):​c.472-89484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,078 control chromosomes in the GnomAD database, including 55,360 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 0.83 (55360 hom., cov: 31)
• Consequence: BACH1 ENST00000422809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219
• Publications: 1 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]

LOC105372770 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372770	XR_007067840.1	n.*69A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000422809.5	c.472-89484T>C		intron_variant	Intron 2 of 4	5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.325-104742T>C		intron_variant	Intron 2 of 3	3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125928 AN: 151960 Hom.: 55366 Cov.: 31

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.828 AC: 125950 AN: 152078 Hom.: 55360 Cov.: 31 AF XY: 0.831 AC XY: 61792 AN XY: 74340

African (AFR) AF: 0.504 AC: 20845 AN: 41396

American (AMR) AF: 0.879 AC: 13446 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 3339 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4359 AN: 5176

South Asian (SAS) AF: 0.958 AC: 4610 AN: 4814

European-Finnish (FIN) AF: 0.969 AC: 10283 AN: 10614

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66066 AN: 67996

Other (OTH) AF: 0.866 AC: 1827 AN: 2110

Alfa AF: 0.867 Hom.: 7718

Bravo AF: 0.807

Asia WGS AF: 0.852 AC: 2964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.9
DANN	Benign	0.84
PhyloP100		0.22

Splicing

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

Other links and lift over

dbSNP: rs2211887; hg19: chr21-30865148;