NM_007294.4:c.548-17G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_007294.4(BRCA1):c.548-17G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,606,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

BRCA1
NM_007294.4 intron

Scores

Clinical Significance

Benign reviewed by expert panel U:1B:21

Conservation

PhyloP100: 0.773

Publications

4 publications found

Variant links:

Genes affected

BRCA1 (HGNC:1100): (BRCA1 DNA repair associated) This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2020]

BRCA1 Gene-Disease associations (from GenCC):

BRCA1-related cancer predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
breast-ovarian cancer, familial, susceptibility to, 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
Fanconi anemia, complementation group S
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
pancreatic cancer, susceptibility to, 4
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
hereditary breast ovarian cancer syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BRCA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-43097306-C-A is Benign according to our data. Variant chr17-43097306-C-A is described in ClinVar as Benign. ClinVar VariationId is 37675.Status of the report is reviewed_by_expert_panel, 3 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007294.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRCA1	NM_007294.4	MANE Select	c.548-17G>T	intron	N/A	NP_009225.1	P38398-1
BRCA1	NM_001407581.1		c.548-17G>T	intron	N/A	NP_001394510.1	A0A2R8Y7V5
BRCA1	NM_001407582.1		c.548-17G>T	intron	N/A	NP_001394511.1	A0A2R8Y7V5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRCA1	ENST00000357654.9	TSL:1 MANE Select	c.548-17G>T	intron	N/A	ENSP00000350283.3	P38398-1
BRCA1	ENST00000471181.7	TSL:1	c.548-17G>T	intron	N/A	ENSP00000418960.2	P38398-7
BRCA1	ENST00000470026.6	TSL:1	c.548-17G>T	intron	N/A	ENSP00000419274.2	P38398-1

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

151628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000953

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000545

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000208

AC:

AN:

249716

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.0000635

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000363

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000291

AC:

423

AN:

1455046

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

204

AN XY:

724256

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33304

American (AMR)

AF:

0.0000224

AC:

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.000256

AC:

AN:

85922

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.000335

AC:

371

AN:

1106304

Other (OTH)

AF:

0.000416

AC:

AN:

60134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000270

AC:

AN:

151746

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74118

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41434

American (AMR)

AF:

0.0000657

AC:

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.0000953

AC:

AN:

10492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000545

AC:

AN:

67930

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000283

Hom.:

Bravo

AF:

0.000257

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

Breast-ovarian cancer, familial, susceptibility to, 1 (7)

not specified (7)

not provided (3)

Hereditary cancer-predisposing syndrome (2)

Breast and/or ovarian cancer (1)

Familial cancer of breast (1)

Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.2

(source)

DANN

Benign

0.35

PhyloP100

0.77

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over