21-29326632-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001186.4(BACH1):c.808T>G(p.Cys270Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,613,872 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (6 hom.)
• Consequence: BACH1 NM_001186.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.22

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014001578).
• BP6: Variant 21-29326632-T-G is Benign according to our data. Variant chr21-29326632-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3040143.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BACH1	NM_001186.4	c.808T>G	p.Cys270Gly	missense_variant	3/5	ENST00000286800.8
BACH1	NM_206866.3	c.808T>G	p.Cys270Gly	missense_variant	3/5
BACH1	NR_027655.3	n.987T>G		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BACH1	ENST00000286800.8	c.808T>G	p.Cys270Gly	missense_variant	3/5	1	NM_001186.4	P1
BACH1	ENST00000399921.5	c.808T>G	p.Cys270Gly	missense_variant	3/5	1		P1

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 151868 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000460

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00271

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00138 AC: 346 AN: 251198 Hom.: 0 AF XY: 0.00135 AC XY: 183 AN XY: 135858

Gnomad AFR exome AF: 0.000494

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00267

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00242 AC: 3537 AN: 1461886 Hom.: 6 Cov.: 31 AF XY: 0.00239 AC XY: 1740 AN XY: 727242

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.000648

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.00300

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.00142 AC: 216 AN: 151986 Hom.: 1 Cov.: 33 AF XY: 0.00129 AC XY: 96 AN XY: 74276

Gnomad4 AFR AF: 0.000459

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.00271

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00195 Hom.: 1

Bravo AF: 0.00149

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00244 AC: 21

ExAC AF: 0.00123 AC: 149

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

BACH1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 16, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.27
Cadd	Benign	15
Dann	Benign	0.69
DEOGEN2	Uncertain	0.63	D;D
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.61	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.014	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.0	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Benign	0.093
Sift	Uncertain	0.010	D;D
Sift4G	Benign	0.45	T;T
Polyphen		0.0060	B;B
Vest4		0.58
MVP		0.47
MPC		0.15
ClinPred		0.063	T
GERP RS		4.5
Varity_R		0.28
gMVP		0.37

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: rs61735774; hg19: chr21-30698953;