chr21-29342277-G-A

Position:

• chr21-29342277-G-A

Variant summary

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

The ENST00000286800.8(BACH1):​c.1777-122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 993,708 control chromosomes in the GnomAD database, including 61,324 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 0.36 (10567 hom., cov: 32)
  • Exomes 𝑓: 0.34 (50757 hom.)
• Consequence: BACH1 ENST00000286800.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACH1	NM_001186.4	c.1777-122G>A		intron_variant		ENST00000286800.8	NP_001177.1
BACH1	NM_206866.3	c.1777-122G>A		intron_variant			NP_996749.1
BACH1	NR_027655.3	n.1956-9357G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000286800.8	c.1777-122G>A		intron_variant		1	NM_001186.4	ENSP00000286800	P1
BACH1	ENST00000399921.5	c.1777-122G>A		intron_variant		1		ENSP00000382805	P1
BACH1	ENST00000422809.5	c.472+12584G>A		intron_variant		5		ENSP00000416569
BACH1	ENST00000468059.1	c.325+12584G>A		intron_variant		3		ENSP00000470673

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55215 AN: 151960 Hom.: 10563 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.339 AC: 285032 AN: 841628 Hom.: 50757 AF XY: 0.339 AC XY: 144323 AN XY: 425614

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.0720

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.363 AC: 55242 AN: 152080 Hom.: 10567 Cov.: 32 AF XY: 0.358 AC XY: 26574 AN XY: 74326

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.0574

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.374

Alfa AF: 0.365 Hom.: 5615

Bravo AF: 0.357

Asia WGS AF: 0.226 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.4
DANN	Benign	0.79

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: rs411697; hg19: chr21-30714598;