chr21-29345416-T-C

Position:

• chr21-29345416-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.*2583T>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 0.525 in 152,020 control chromosomes in the GnomAD database, including 21,413 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 0.53 (21413 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: BACH1 NM_001186.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACH1	NM_001186.4	c.*2583T>C		3_prime_UTR_variant	5/5	ENST00000286800.8	NP_001177.1
BACH1	NM_206866.3	c.*2583T>C		3_prime_UTR_variant	5/5		NP_996749.1
BACH1	NR_027655.3	n.1956-6218T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000286800.8	c.*2583T>C		3_prime_UTR_variant	5/5	1	NM_001186.4	ENSP00000286800.3
BACH1	ENST00000399921.5	c.*2583T>C		3_prime_UTR_variant	5/5	1		ENSP00000382805.1
BACH1	ENST00000422809.5	c.471+15723T>C		intron_variant		5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.324+15723T>C		intron_variant		3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79804 AN: 151894 Hom.: 21383 Cov.: 33

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 FIN exome AF: 0.250

GnomAD4 genome AF: 0.525 AC: 79873 AN: 152012 Hom.: 21413 Cov.: 33 AF XY: 0.523 AC XY: 38830 AN XY: 74284

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.528

Alfa AF: 0.494 Hom.: 33933

Bravo AF: 0.533

Asia WGS AF: 0.561 AC: 1945 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs372883; hg19: chr21-30717737;