chr21-29342954-T-C

Position:

• chr21-29342954-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
BACH1	NM_001186.4	c.*121T>C		3_prime_UTR_variant	5/5	ENST00000286800.8	NP_001177.1
BACH1	NM_206866.3	c.*121T>C		3_prime_UTR_variant	5/5		NP_996749.1
BACH1	NR_027655.3	n.1956-8680T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000286800.8	c.*121T>C		3_prime_UTR_variant	5/5	1	NM_001186.4	ENSP00000286800	P1
BACH1	ENST00000399921.5	c.*121T>C		3_prime_UTR_variant	5/5	1		ENSP00000382805	P1
BACH1	ENST00000422809.5	c.472+13261T>C		intron_variant		5		ENSP00000416569
BACH1	ENST00000468059.1	c.325+13261T>C		intron_variant		3		ENSP00000470673

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

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.501

Gnomad4 ASJ exome AF: 0.464

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.413

Gnomad4 OTH exome AF: 0.453

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

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.485

Alfa AF: 0.441 Hom.: 19258

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs425989; hg19: chr21-30715275;