chr19-19182655-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145784.2(BORCS8):c.244G>A(p.Val82Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,550,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

BORCS8
NM_001145784.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0150

Publications

0 publications found

Variant links:

Genes affected

BORCS8 (HGNC:37247): (BLOC-1 related complex subunit 8) Involved in heart development. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

BORCS8 links:

BORCS8-MEF2B (HGNC:39979): (BORCS8-MEF2B readthrough) This gene represents numerous read-through transcripts that span GeneID:729991 and 100271849. Many read-through transcripts are predicted to be nonsense-mediated decay (NMD) candidates, and are thought to be non-coding. Some transcripts are predicted to be capable of translation reinitiation at a downstream AUG, resulting in expression of at least one isoform of myocyte enhancer factor 2B (MEF2B) from this read-through locus. At least one additional MEF2B variant and isoform can be expressed from a downstream promoter, and is annotated on GeneID:100271849. [provided by RefSeq, Oct 2010]

BORCS8-MEF2B links:

MEF2B (HGNC:6995): (myocyte enhancer factor 2B) The product of this gene is a member of the MADS/MEF2 family of DNA binding proteins. The protein is thought to regulate gene expression, including expression of the smooth muscle myosin heavy chain gene. This region undergoes considerable alternative splicing, with transcripts supporting two non-overlapping loci (GeneID 729991 and 100271849) as well as numerous read-through transcripts that span both loci (annotated as GeneID 4207). Several isoforms of this protein are expressed from either this locus or from some of the read-through transcripts annotated on GeneID 4207. [provided by RefSeq, Jan 2014]

MEF2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0605025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145784.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BORCS8	NM_001145784.2	MANE Select	c.244G>A	p.Val82Ile	missense	Exon 4 of 6	NP_001139256.1	Q96FH0-1
BORCS8	NM_001145783.2		c.244G>A	p.Val82Ile	missense	Exon 4 of 4	NP_001139255.1	Q96FH0-2
BORCS8-MEF2B	NM_005919.4		c.-188G>A		5_prime_UTR	Exon 2 of 10	NP_005910.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BORCS8	ENST00000462790.8	TSL:1 MANE Select	c.244G>A	p.Val82Ile	missense	Exon 4 of 6	ENSP00000425864.1	Q96FH0-1
BORCS8	ENST00000477565.3	TSL:1	c.244G>A	p.Val82Ile	missense	Exon 4 of 4	ENSP00000424833.1	Q96FH0-2
BORCS8-MEF2B	ENST00000514819.7	TSL:5	c.-61G>A		5_prime_UTR	Exon 2 of 9	ENSP00000454967.3	H3BNR1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000263

AC:

AN:

152348

AF XY:

0.0000247

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000811

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000658

AC:

AN:

1398916

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

689964

show subpopulations

African (AFR)

AF:

0.0000949

AC:

AN:

31596

American (AMR)

AF:

0.0000840

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.0000397

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35730

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000760

AC:

AN:

1078874

Other (OTH)

AF:

0.0000345

AC:

AN:

57988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41392

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000388

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000422

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.66

M_CAP

Benign

0.0041

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

PhyloP100

0.015

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.52

REVEL

Benign

0.017

Sift

Benign

0.19

Sift4G

Benign

0.19

Polyphen

0.060

Vest4

0.058

MVP

0.048

ClinPred

0.058

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.24

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over