Variant chr21-29326632-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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 (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 6 hom. )

Consequence

BACH1
NM_001186.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.22

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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 no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BACH1	NM_001186.4 linkuse as main transcript	c.808T>G	p.Cys270Gly	missense_variant	3/5	ENST00000286800.8
BACH1	NM_206866.3 linkuse as main transcript	c.808T>G	p.Cys270Gly	missense_variant	3/5
BACH1	NR_027655.3 linkuse as main transcript	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 linkuse as main transcript	c.808T>G	p.Cys270Gly	missense_variant	3/5	1	NM_001186.4	P1
BACH1	ENST00000399921.5 linkuse as main transcript	c.808T>G	p.Cys270Gly	missense_variant	3/5	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

216

AN:

151868

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00135

AC XY:

183

AN XY:

135858

show subpopulations

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.:

Cov.:

AF XY:

0.00239

AC XY:

1740

AN XY:

727242

show subpopulations

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.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74276

show subpopulations

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.:

Bravo

AF:

0.00149

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00123

AC:

149

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BACH1-related disorder

Benign:1

Likely benign, no assertion criteria provided

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

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Uncertain

0.63

D;D

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over