rs388707

Variant names:

• chr21-29342455-T-C
• rs388707
• NM_001186.4:c.1833T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001186.4(BACH1):​c.1833T>C​(p.Gly611Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,613,806 control chromosomes in the GnomAD database, including 161,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.49 (19501 hom., cov: 33)
  • Exomes 𝑓: 0.44 (141877 hom.)
• Consequence: BACH1 NM_001186.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.61
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 21-29342455-T-C is Benign according to our data. Variant chr21-29342455-T-C is described in ClinVar as [Benign]. Clinvar id is 3059943.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH1	NM_001186.4	c.1833T>C	p.Gly611Gly	synonymous_variant	Exon 5 of 5	ENST00000286800.8	NP_001177.1
BACH1	NM_206866.3	c.1833T>C	p.Gly611Gly	synonymous_variant	Exon 5 of 5		NP_996749.1
BACH1	NR_027655.3	n.1956-9179T>C		intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000286800.8	c.1833T>C	p.Gly611Gly	synonymous_variant	Exon 5 of 5	1	NM_001186.4	ENSP00000286800.3
BACH1	ENST00000399921.5	c.1833T>C	p.Gly611Gly	synonymous_variant	Exon 5 of 5	1		ENSP00000382805.1
BACH1	ENST00000422809.5	c.471+12762T>C		intron_variant	Intron 2 of 4	5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.324+12762T>C		intron_variant	Intron 2 of 3	3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75020 AN: 151886 Hom.: 19476 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.489

GnomAD2 exomes AF: 0.470 AC: 117996 AN: 251236 AF XY: 0.468

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.525

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.463

Gnomad FIN exome AF: 0.378

Gnomad NFE exome AF: 0.417

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.436 AC: 637340 AN: 1461802 Hom.: 141877 Cov.: 59 AF XY: 0.439 AC XY: 319247 AN XY: 727204

African (AFR) AF: 0.654 AC: 21908 AN: 33478

American (AMR) AF: 0.519 AC: 23234 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 12110 AN: 26136

East Asian (EAS) AF: 0.451 AC: 17884 AN: 39698

South Asian (SAS) AF: 0.571 AC: 49272 AN: 86250

European-Finnish (FIN) AF: 0.369 AC: 19733 AN: 53414

Middle Eastern (MID) AF: 0.429 AC: 2474 AN: 5766

European-Non Finnish (NFE) AF: 0.416 AC: 463114 AN: 1111944

Other (OTH) AF: 0.457 AC: 27611 AN: 60392

GnomAD4 genome AF: 0.494 AC: 75090 AN: 152004 Hom.: 19501 Cov.: 33 AF XY: 0.492 AC XY: 36567 AN XY: 74290

African (AFR) AF: 0.647 AC: 26804 AN: 41454

American (AMR) AF: 0.490 AC: 7481 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1615 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2390 AN: 5168

South Asian (SAS) AF: 0.596 AC: 2869 AN: 4816

European-Finnish (FIN) AF: 0.372 AC: 3921 AN: 10554

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28579 AN: 67966

Other (OTH) AF: 0.491 AC: 1033 AN: 2106

Alfa AF: 0.452 Hom.: 25317

Bravo AF: 0.506

Asia WGS AF: 0.555 AC: 1928 AN: 3478

EpiCase AF: 0.436

EpiControl AF: 0.423

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

BACH1-related disorder Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.17
DANN	Benign	0.72
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs388707; hg19: chr21-30714776; COSMIC: COSV54517887;