rs141173428

Variant names:

• chr6-136278253-C-T
• rs141173428
• NM_014739.3:c.628G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-136278253-C-T
• chr6-136278253-C-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_014739.3(BCLAF1):​c.628G>A​(p.Gly210Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000163 in 1,603,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00098 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000080 (0 hom.)
• Consequence: BCLAF1 NM_014739.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.13
• Publications: 9 publications found

Genes affected

BCLAF1 (HGNC:16863): (BCL2 associated transcription factor 1) This gene encodes a transcriptional repressor that interacts with several members of the BCL2 family of proteins. Overexpression of this protein induces apoptosis, which can be suppressed by co-expression of BCL2 proteins. The protein localizes to dot-like structures throughout the nucleus, and redistributes to a zone near the nuclear envelope in cells undergoing apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0066773593).
• BP6: Variant 6-136278253-C-T is Benign according to our data. Variant chr6-136278253-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 402423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014739.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCLAF1	NM_014739.3	MANE Select	c.628G>A	p.Gly210Ser	missense	Exon 4 of 13	NP_055554.1	Q9NYF8-1
	BCLAF1	NM_001386700.1		c.628G>A	p.Gly210Ser	missense	Exon 5 of 14	NP_001373629.1	Q9NYF8-1
	BCLAF1	NM_001386701.1		c.628G>A	p.Gly210Ser	missense	Exon 5 of 14	NP_001373630.1	Q9NYF8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCLAF1	ENST00000531224.6	TSL:1 MANE Select	c.628G>A	p.Gly210Ser	missense	Exon 4 of 13	ENSP00000435210.1	Q9NYF8-1
	BCLAF1	ENST00000527759.5	TSL:1	c.622G>A	p.Gly208Ser	missense	Exon 4 of 13	ENSP00000434826.1	Q9NYF8-2
	BCLAF1	ENST00000530767.5	TSL:1	c.628G>A	p.Gly210Ser	missense	Exon 4 of 13	ENSP00000436501.1	Q9NYF8-4

Frequencies

GnomAD3 genomes AF: 0.000976 AC: 146 AN: 149540 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000339

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00120

Gnomad ASJ AF: 0.000879

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00336

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.000491

GnomAD2 exomes AF: 0.0104 AC: 2550 AN: 246102 AF XY: 0.0103

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00580

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0276

Gnomad NFE exome AF: 0.0137

Gnomad OTH exome AF: 0.0112

GnomAD4 exome AF: 0.0000798 AC: 116 AN: 1453836 Hom.: 0 Cov.: 32 AF XY: 0.0000719 AC XY: 52 AN XY: 723224

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000598 AC: 2 AN: 33450

American (AMR) AF: 0.0000449 AC: 2 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86178

European-Finnish (FIN) AF: 0.00178 AC: 92 AN: 51562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.0000154 AC: 17 AN: 1106622

Other (OTH) AF: 0.0000166 AC: 1 AN: 60088

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000976 AC: 146 AN: 149658 Hom.: 0 Cov.: 32 AF XY: 0.00115 AC XY: 84 AN XY: 73152

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000338 AC: 14 AN: 41460

American (AMR) AF: 0.00120 AC: 18 AN: 15032

Ashkenazi Jewish (ASJ) AF: 0.000879 AC: 3 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00336 AC: 34 AN: 10120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00113 AC: 75 AN: 66378

Other (OTH) AF: 0.000485 AC: 1 AN: 2060

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00453 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0201 AC: 2445

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0067	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.74	N
PhyloP100		4.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.53
ClinPred		0.016	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.52
Mutation Taster		=74/26	polymorphism

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: rs141173428; hg19: chr6-136599391; COSMIC: COSV62140674; COSMIC: COSV62140674;