Genetic Variant NM_017622.3:c.765A>C (chr17-8189376-T-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017622.3(BORCS6):c.765A>C(p.Pro255Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 1,601,868 control chromosomes in the GnomAD database, including 507,586 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.73 ( 42214 hom., cov: 33)

Exomes 𝑓: 0.79 ( 465372 hom. )

Consequence

BORCS6
NM_017622.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0490

Publications

19 publications found

Variant links:

Genes affected

BORCS6 (HGNC:25939): (BLOC-1 related complex subunit 6) Enables identical protein binding activity. Involved in lysosome localization. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

BORCS6 links:

ENSG00000279152 (HGNC:):

ENSG00000279152 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP7

Synonymous conserved (PhyloP=-0.049 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS6	NM_017622.3 link	c.765A>C	p.Pro255Pro	synonymous_variant	Exon 1 of 1	ENST00000389017.6	NP_060092.2	Q96GS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BORCS6	ENST00000389017.6 link	c.765A>C	p.Pro255Pro	synonymous_variant	Exon 1 of 1	6	NM_017622.3	ENSP00000373669.4	Q96GS4
ENSG00000279152	ENST00000622992.1 link	n.444T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000299228	ENST00000761712.1 link	n.-108T>G		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.733

AC:

111438

AN:

152004

Hom.:

42186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.669

Gnomad AMI

AF:

0.789

Gnomad AMR

AF:

0.554

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.783

Gnomad FIN

AF:

0.856

Gnomad MID

AF:

0.640

Gnomad NFE

AF:

0.829

Gnomad OTH

AF:

0.711

GnomAD2 exomes

AF:

0.707

AC:

161089

AN:

227730

AF XY:

0.727

show subpopulations

Gnomad AFR exome

AF:

0.657

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.629

Gnomad EAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.853

Gnomad NFE exome

AF:

0.830

Gnomad OTH exome

AF:

0.729

GnomAD4 exome

AF:

0.792

AC:

1148315

AN:

1449748

Hom.:

465372

Cov.:

AF XY:

0.794

AC XY:

571981

AN XY:

720474

show subpopulations

African (AFR)

AF:

0.655

AC:

21686

AN:

33104

American (AMR)

AF:

0.417

AC:

17745

AN:

42524

Ashkenazi Jewish (ASJ)

AF:

0.627

AC:

16209

AN:

25836

East Asian (EAS)

AF:

0.288

AC:

11233

AN:

39000

South Asian (SAS)

AF:

0.795

AC:

67705

AN:

85142

European-Finnish (FIN)

AF:

0.858

AC:

44688

AN:

52056

Middle Eastern (MID)

AF:

0.686

AC:

3936

AN:

5736

European-Non Finnish (NFE)

AF:

0.832

AC:

920161

AN:

1106478

Other (OTH)

AF:

0.751

AC:

44952

AN:

59872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

14462

28924

43386

57848

72310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20676

41352

62028

82704

103380

<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:

0.733

AC:

111508

AN:

152120

Hom.:

42214

Cov.:

AF XY:

0.730

AC XY:

54263

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.669

AC:

27740

AN:

41476

American (AMR)

AF:

0.553

AC:

8457

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

2132

AN:

3470

East Asian (EAS)

AF:

0.299

AC:

1541

AN:

5150

South Asian (SAS)

AF:

0.786

AC:

3791

AN:

4826

European-Finnish (FIN)

AF:

0.856

AC:

9075

AN:

10600

Middle Eastern (MID)

AF:

0.641

AC:

186

AN:

290

European-Non Finnish (NFE)

AF:

0.829

AC:

56382

AN:

67992

Other (OTH)

AF:

0.704

AC:

1484

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1448

2896

4344

5792

7240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.786

Hom.:

92353

Bravo

AF:

0.702

Asia WGS

AF:

0.573

AC:

1996

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

-0.049

Mutation Taster

=97/3

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over