rs1555618429

chr17-61859888-C-Gchr17-61859888-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032043.3(BRIP1):c.113G>C(p.Ser38Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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. S38N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRIP1 NM_032043.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

Genes affected

BRIP1 (HGNC:20473): (BRCA1 interacting helicase 1) The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09923029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3	c.113G>C	p.Ser38Thr	missense_variant	3/20	ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7	c.113G>C	p.Ser38Thr	missense_variant	3/20	1	NM_032043.3	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	19
Dann	Benign	0.83
DEOGEN2	Benign	0.10	T;.;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.070
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.099	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N;N;.
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.57	N;.;.
REVEL	Benign	0.035
Sift	Benign	0.37	T;.;.
Sift4G	Benign	0.60	T;T;.
Polyphen		0.19	B;.;.
Vest4		0.24
MutPred		0.29		Loss of disorder (P = 0.0853);Loss of disorder (P = 0.0853);Loss of disorder (P = 0.0853);
MVP		0.53
MPC		0.16
ClinPred		0.13	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.042
gMVP		0.33

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: chr17-59937249;