21-29516557-G-A

Variant names:

• chr21-29516557-G-A
• rs7275620
• ENST00000422809.5:c.472-65755G>A

Variant summary

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

The ENST00000422809.5(BACH1):​c.472-65755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 152,266 control chromosomes in the GnomAD database, including 131 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 0.036 (131 hom., cov: 32)
• Consequence: BACH1 ENST00000422809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422809.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACH1	ENST00000422809.5	TSL:5	c.472-65755G>A		intron	N/A	ENSP00000416569.1
	BACH1	ENST00000468059.1	TSL:3	c.325-81013G>A		intron	N/A	ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5452 AN: 152148 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0315

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

GnomAD4 genome AF: 0.0360 AC: 5475 AN: 152266 Hom.: 131 Cov.: 32 AF XY: 0.0377 AC XY: 2808 AN XY: 74454

African (AFR) AF: 0.0330 AC: 1371 AN: 41552

American (AMR) AF: 0.0675 AC: 1032 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.121 AC: 624 AN: 5176

South Asian (SAS) AF: 0.0419 AC: 202 AN: 4824

European-Finnish (FIN) AF: 0.0313 AC: 333 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0265 AC: 1802 AN: 68020

Other (OTH) AF: 0.0341 AC: 72 AN: 2114

Alfa AF: 0.0294 Hom.: 165

Bravo AF: 0.0383

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.24
PhyloP100		0.019

Splicing

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

Other links and lift over

dbSNP: rs7275620; hg19: chr21-30888877;