17-61799240-G-C

Variant names:

• chr17-61799240-G-C
• rs1555607173
• NM_032043.3:c.1200C>G
• BRIP1 p.Asp400Glu

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+1 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 1 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_ModerateB3_Supporting

The NM_032043.3(BRIP1):c.1200C>G (p.Asp400Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The gene BRIP1 is a tumor suppressor gene (CancerMine: 11 TSG, 4 oncogene, 1 driver citations). The gene BRIP1 is a known oncogene (CancerMine: 11 TSG, 4 oncogene, 1 driver citations). The gene BRIP1 is a cancer driver gene (CancerMine: 11 TSG, 4 oncogene, 1 driver citations). The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.D400= (synonymous): Likely_benign (ClinVar VariationId 530370, 1 star); p.D400Y: Uncertain_significance (ClinVar VariationId 216785, 2 stars)

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRIP1 NM_032043.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.821
• Publications: 0 publications found

Genes affected

BRIP1 (HGNC:20473): (BRCA1 interacting DNA 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]

BRIP1 Gene-Disease associations (from GenCC):

• familial ovarian cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Fanconi anemia

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
• Fanconi anemia complementation group J

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])
	B3Computational evidence does not support deleterious effect		Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_032043.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	BRIP1 NM_032043.3	MANE Select	c.1200C>G p.Asp400Glu	missense	Exon 9 of 20	Prot: NP_114432.2 UniProt:

BRIP1 NM_032043.3

MANE Select

HGVSc / HGVSpc.1200C>Gp.Asp400Glu

Exon rankExon 9 of 20

missense

Prot: NP_114432.2UniProt: Q9BX63-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	BRIP1 ENST00000259008.7	TSL:1MANE Select	c.1200C>G p.Asp400Glu	missense	Exon 9 of 20	Prot: ENSP00000259008.2 UniProt:
	BRIP1 ENST00000682453.1		c.1200C>G p.Asp400Glu	missense	Exon 10 of 21	Prot: ENSP00000506943.1 UniProt:
	BRIP1 ENST00000683039.1		c.1200C>G p.Asp400Glu	missense	Exon 10 of 21	Prot: ENSP00000508303.1 UniProt:

BRIP1 ENST00000259008.7

TSL:1MANE Select

HGVSc / HGVSpc.1200C>Gp.Asp400Glu

Exon rankExon 9 of 20

missense

Prot: ENSP00000259008.2UniProt: Q9BX63-1

BRIP1 ENST00000682453.1

HGVSc / HGVSpc.1200C>Gp.Asp400Glu

Exon rankExon 10 of 21

missense

Prot: ENSP00000506943.1UniProt: Q9BX63-1

BRIP1 ENST00000683039.1

HGVSc / HGVSpc.1200C>Gp.Asp400Glu

Exon rankExon 10 of 21

missense

Prot: ENSP00000508303.1UniProt: Q9BX63-1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	15
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.91	D
FuncVEP CTI	Benign	0.14
GPN-Star LLR	N/A	-3.3
GPN-Star score	N/A	3.3
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100	Benign	0.82
popEVE	Benign	-3.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.4	D
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.7
REVEL	Benign	0.17
Sift	Benign	0.10	T
Sift4G	Benign	0.091	T
Varity_R	N/A	0.29
VESM-3B	Benign	-11

Showing 29 of 29 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.010	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs1555607173;

hg19: chr17-59876601;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar