rs425989

Variant names:

• chr21-29342954-T-C
• rs425989
• NM_001186.4:c.*121T>C

Variant summary

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

The NM_001186.4(BACH1):​c.*121T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 966,464 control chromosomes in the GnomAD database, including 96,339 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 0.49 (18803 hom., cov: 32)
  • Exomes 𝑓: 0.43 (77536 hom.)
• Consequence: BACH1 NM_001186.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605
• Publications: 17 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH1	NM_001186.4	c.*121T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000286800.8	NP_001177.1
BACH1	NM_206866.3	c.*121T>C		3_prime_UTR_variant	Exon 5 of 5		NP_996749.1
BACH1	NR_027655.3	n.1956-8680T>C		intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000286800.8	c.*121T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_001186.4	ENSP00000286800.3
BACH1	ENST00000399921.5	c.*121T>C		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000382805.1
BACH1	ENST00000422809.5	c.471+13261T>C		intron_variant	Intron 2 of 4	5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.324+13261T>C		intron_variant	Intron 2 of 3	3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73922 AN: 151964 Hom.: 18779 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.430 AC: 350029 AN: 814380 Hom.: 77536 Cov.: 10 AF XY: 0.433 AC XY: 174167 AN XY: 402252

African (AFR) AF: 0.622 AC: 12125 AN: 19502

American (AMR) AF: 0.501 AC: 8312 AN: 16592

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 6981 AN: 15056

East Asian (EAS) AF: 0.451 AC: 14482 AN: 32106

South Asian (SAS) AF: 0.569 AC: 22060 AN: 38794

European-Finnish (FIN) AF: 0.367 AC: 11027 AN: 30046

Middle Eastern (MID) AF: 0.426 AC: 1182 AN: 2772

European-Non Finnish (NFE) AF: 0.413 AC: 256959 AN: 622196

Other (OTH) AF: 0.453 AC: 16901 AN: 37316

GnomAD4 genome AF: 0.487 AC: 73990 AN: 152084 Hom.: 18803 Cov.: 32 AF XY: 0.485 AC XY: 36036 AN XY: 74340

African (AFR) AF: 0.621 AC: 25735 AN: 41466

American (AMR) AF: 0.488 AC: 7454 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2387 AN: 5176

South Asian (SAS) AF: 0.596 AC: 2876 AN: 4828

European-Finnish (FIN) AF: 0.370 AC: 3915 AN: 10574

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28585 AN: 67974

Other (OTH) AF: 0.485 AC: 1025 AN: 2114

Alfa AF: 0.447 Hom.: 24916

Bravo AF: 0.498

Asia WGS AF: 0.554 AC: 1927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.72
PhyloP100		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs425989; hg19: chr21-30715275; COSMIC: COSV106057351;