10-125823589-A-G

Position:

• chr10-125823589-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_078468.3(BCCIP):​c.32A>G​(p.Glu11Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: BCCIP NM_078468.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0390

Genes affected

BCCIP (HGNC:978): (BRCA2 and CDKN1A interacting protein) This gene product was isolated on the basis of its interaction with BRCA2 and p21 proteins. It is an evolutionarily conserved nuclear protein with multiple interacting domains. The N-terminal half shares moderate homology with regions of calmodulin and M-calpain, suggesting that it may also bind calcium. Functional studies indicate that this protein may be an important cofactor for BRCA2 in tumor suppression, and a modulator of CDK2 kinase activity via p21. This protein has also been implicated in the regulation of BRCA2 and RAD51 nuclear focus formation, double-strand break-induced homologous recombination, and cell cycle progression. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

BCCIP (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035295486).
• BP6: Variant 10-125823589-A-G is Benign according to our data. Variant chr10-125823589-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2314197.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCCIP	NM_078468.3	c.32A>G	p.Glu11Gly	missense_variant	1/7	ENST00000278100.11	NP_510868.1
BCCIP	NM_016567.4	c.32A>G	p.Glu11Gly	missense_variant	1/8		NP_057651.1
BCCIP	NM_078469.3	c.32A>G	p.Glu11Gly	missense_variant	1/7		NP_510869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCCIP	ENST00000278100.11	c.32A>G	p.Glu11Gly	missense_variant	1/7	1	NM_078468.3	ENSP00000278100.6
BCCIP	ENST00000368759.5	c.32A>G	p.Glu11Gly	missense_variant	1/8	1		ENSP00000357748.5
BCCIP	ENST00000299130.7	c.32A>G	p.Glu11Gly	missense_variant	1/7	1		ENSP00000299130.3
BCCIP	ENST00000463330.5	n.-21A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248898 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461726 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 727172

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74350

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.89
DANN	Benign	0.55
DEOGEN2	Benign	0.017	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.035	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.49	N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.22	N;N;N
REVEL	Benign	0.028
Sift	Benign	0.99	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.068
MutPred		0.15		Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);
MVP		0.10
MPC		0.11
ClinPred		0.039	T
GERP RS		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.027
gMVP		0.066

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

LitVar

Other links and lift over

dbSNP: rs1010143629; hg19: chr10-127512158;