rs873651

Variant names:

• chr21-29409528-G-A
• rs873651
• ENST00000422809.5:c.471+79835G>A

Variant summary

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

The ENST00000422809.5(BACH1):​c.471+79835G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,082 control chromosomes in the GnomAD database, including 9,341 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 0.31 (9341 hom., cov: 32)
• Consequence: BACH1 ENST00000422809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.425 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.471+79835G>A		intron_variant	Intron 2 of 4	5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.324+79835G>A		intron_variant	Intron 2 of 3	3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47555 AN: 151962 Hom.: 9341 Cov.: 32

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.313 AC: 47550 AN: 152082 Hom.: 9341 Cov.: 32 AF XY: 0.314 AC XY: 23354 AN XY: 74310

African (AFR) AF: 0.0810 AC: 3363 AN: 41530

American (AMR) AF: 0.348 AC: 5319 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1432 AN: 3472

East Asian (EAS) AF: 0.136 AC: 705 AN: 5178

South Asian (SAS) AF: 0.360 AC: 1732 AN: 4812

European-Finnish (FIN) AF: 0.428 AC: 4507 AN: 10540

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29132 AN: 67962

Other (OTH) AF: 0.333 AC: 705 AN: 2114

Alfa AF: 0.280 Hom.: 3278

Bravo AF: 0.294

Asia WGS AF: 0.219 AC: 759 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.75
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs873651; hg19: chr21-30781848;