21-29343164-A-G

Position:

• chr21-29343164-A-G

Variant summary

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

The NM_001186.4(BACH1):​c.*331A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 175,630 control chromosomes in the GnomAD database, including 234 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 0.027 (197 hom., cov: 32)
  • Exomes 𝑓: 0.020 (37 hom.)
• Consequence: BACH1 NM_001186.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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]

BACH1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACH1	NM_001186.4	c.*331A>G		3_prime_UTR_variant	5/5	ENST00000286800.8	NP_001177.1
BACH1	NM_206866.3	c.*331A>G		3_prime_UTR_variant	5/5		NP_996749.1
BACH1	NR_027655.3	n.1956-8470A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000286800.8	c.*331A>G		3_prime_UTR_variant	5/5	1	NM_001186.4	ENSP00000286800.3
BACH1	ENST00000399921.5	c.*331A>G		3_prime_UTR_variant	5/5	1		ENSP00000382805.1
BACH1	ENST00000422809.5	c.471+13471A>G		intron_variant		5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.324+13471A>G		intron_variant		3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4164 AN: 152222 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0597

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.0206

GnomAD4 exome AF: 0.0201 AC: 468 AN: 23290 Hom.: 37 Cov.: 0 AF XY: 0.0190 AC XY: 230 AN XY: 12082

Gnomad4 AFR exome AF: 0.0647

Gnomad4 AMR exome AF: 0.0393

Gnomad4 ASJ exome AF: 0.00147

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.00305

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.0198

GnomAD4 genome AF: 0.0275 AC: 4183 AN: 152340 Hom.: 197 Cov.: 32 AF XY: 0.0283 AC XY: 2108 AN XY: 74500

Gnomad4 AFR AF: 0.0599

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.00828

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00156

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.00503 Hom.: 17

Bravo AF: 0.0337

Asia WGS AF: 0.0730 AC: 254 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2070401; hg19: chr21-30715485;