rs779071140

Variant names:

• chr12-111644438-C-A
• NM_006768.5:c.1540G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-111644438-C-A
• chr12-111644438-C-T

Variant summary

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

The NM_006768.5(BRAP):​c.1540G>T​(p.Val514Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,888 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. 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. V514M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BRAP NM_006768.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354

Genes affected

BRAP (HGNC:1099): (BRCA1 associated protein) The protein encoded by this gene was identified by its ability to bind to the nuclear localization signal of BRCA1 and other proteins. It is a cytoplasmic protein which may regulate nuclear targeting by retaining proteins with a nuclear localization signal in the cytoplasm. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036198914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAP	NM_006768.5	c.1540G>T	p.Val514Leu	missense_variant	Exon 12 of 12	ENST00000419234.9	NP_006759.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAP	ENST00000419234.9	c.1540G>T	p.Val514Leu	missense_variant	Exon 12 of 12	1	NM_006768.5	ENSP00000403524.3
BRAP	ENST00000327551.6	c.1450G>T	p.Val484Leu	missense_variant	Exon 12 of 12	1		ENSP00000330813.5
BRAP	ENST00000547043.1	n.1444G>T		non_coding_transcript_exon_variant	Exon 8 of 8	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.17
DANN	Benign	0.52
DEOGEN2	Benign	0.30	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.29	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.41	N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.0080
Sift	Benign	0.32	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;.
Vest4		0.056
MutPred		0.30		Loss of helix (P = 0.0795);.;
MVP		0.42
MPC		0.13
ClinPred		0.090	T
GERP RS		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.021
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-112082242; COSMIC: COSV59538321;