NM_032043.3:c.*3113_*3114dupTT

Variant names:

• chr17-61680181-T-TAA
• rs35235448
• NM_032043.3:c.*3113_*3114dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_032043.3(BRIP1):​c.*3113_*3114dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0043 (3 hom., cov: 0)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 2 publications found

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]

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: Illumina, Orphanet
• Fanconi anemia complementation group J

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

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

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00435 (556/127916) while in subpopulation AFR AF = 0.0149 (515/34476). AF 95% confidence interval is 0.0139. There are 3 homozygotes in GnomAd4. There are 251 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	NM_032043.3	MANE Select	c.*3113_*3114dupTT		3_prime_UTR	Exon 20 of 20	NP_114432.2	Q9BX63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	ENST00000259008.7	TSL:1 MANE Select	c.*3113_*3114dupTT		3_prime_UTR	Exon 20 of 20	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000682755.1		c.*3113_*3114dupTT		3_prime_UTR	Exon 18 of 18	ENSP00000507660.1	A0A804HJV4

Frequencies

GnomAD3 genomes AF: 0.00433 AC: 554 AN: 127920 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00247

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000255

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000116

Gnomad OTH AF: 0.00119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00435 AC: 556 AN: 127916 Hom.: 3 Cov.: 0 AF XY: 0.00412 AC XY: 251 AN XY: 60864

African (AFR) AF: 0.0149 AC: 515 AN: 34476

American (AMR) AF: 0.00247 AC: 31 AN: 12554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3140

East Asian (EAS) AF: 0.00 AC: 0 AN: 4400

South Asian (SAS) AF: 0.000257 AC: 1 AN: 3888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.000116 AC: 7 AN: 60286

Other (OTH) AF: 0.00119 AC: 2 AN: 1686

Alfa AF: 0.00 Hom.: 168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61

Splicing

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

Other links and lift over

dbSNP: rs35235448; hg19: chr17-59757542;