dbSNP rs767070482: BORCS7:p.Thr27Asn (chr10-102854366-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001136200.2(BORCS7):c.80C>A(p.Thr27Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,426,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T27I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

BORCS7
NM_001136200.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.31

Publications

0 publications found

Variant links:

Genes affected

BORCS7 (HGNC:23516): (BLOC-1 related complex subunit 7) Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

BORCS7 links:

BORCS7-ASMT (HGNC:49183): (BORCS7-ASMT readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring C10orf32 (chromosome 10 open reading frame 32) and AS3MT (arsenic, +3 oxidation state, methyltransferase) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

BORCS7-ASMT links:

ENSG00000282772 (HGNC:):

ENSG00000282772 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26879498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS7	NM_001136200.2 link	c.80C>A	p.Thr27Asn	missense_variant	Exon 1 of 5	ENST00000339834.10	NP_001129672.1	Q96B45A0A0B4J1R7
BORCS7	NM_144591.5 link	c.80C>A	p.Thr27Asn	missense_variant	Exon 1 of 6		NP_653192.2	Q96B45A0A0B4J1R7
BORCS7-ASMT	NR_037644.1 link	n.157C>A		non_coding_transcript_exon_variant	Exon 1 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS7	ENST00000339834.10 link	c.80C>A	p.Thr27Asn	missense_variant	Exon 1 of 5	1	NM_001136200.2	ENSP00000342331.5		Q96B45
BORCS7-ASMT	ENST00000299353.6 link	n.80C>A		non_coding_transcript_exon_variant	Exon 1 of 15	5		ENSP00000299353.5		A0A0B4J1R7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426560

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705960

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

33106

American (AMR)

AF:

0.00

AC:

AN:

38798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25404

East Asian (EAS)

AF:

0.00

AC:

AN:

38600

South Asian (SAS)

AF:

0.00

AC:

AN:

81618

European-Finnish (FIN)

AF:

0.0000197

AC:

AN:

50770

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093372

Other (OTH)

AF:

0.00

AC:

AN:

59178

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

0.98

Eigen

Benign

0.077

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.82

PhyloP100

5.3

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.086

Sift

Benign

0.088

T;T

Sift4G

Benign

0.073

T;T

Vest4

0.41

MVP

0.37

MPC

0.20

ClinPred

0.58

GERP RS

5.9

PromoterAI

0.065

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

gMVP

0.27

Mutation Taster

=61/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over