ENST00000515303.2:c.-131G>T

Variant names:

• chr4-83485052-C-A
• rs145796091
• ENST00000515303.2:c.-131G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000515303.2(ABRAXAS1):​c.-131G>T variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABRAXAS1 ENST00000515303.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.272
• Publications: 0 publications found

Genes affected

ABRAXAS1 (HGNC:25829): (abraxas 1, BRCA1 A complex subunit) This gene encodes a protein that binds to the C-terminal repeats of breast cancer 1 (BRCA1) through a phospho-SXXF motif. The encoded protein recruits ubiquitin interaction motif containing 1 protein to BRCA1 protein and is required for DNA damage resistance, DNA repair, and cell cycle checkpoint control. Pseudogenes of this gene are found on chromosomes 3 and 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 4-83485052-C-A is Benign according to our data. Variant chr4-83485052-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1799831.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000515303.2. 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
	ABRAXAS1	NM_139076.3	MANE Select	c.21G>T	p.Ser7Ser	synonymous	Exon 1 of 9	NP_620775.2	Q6UWZ7-1
	ABRAXAS1	NM_001345962.2		c.-240G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001332891.1	Q6UWZ7-2
	ABRAXAS1	NM_001345962.2		c.-240G>T		5_prime_UTR	Exon 1 of 8	NP_001332891.1	Q6UWZ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS1	ENST00000515303.2	TSL:1	c.-131G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000421068.1	E9PHB9
	ABRAXAS1	ENST00000321945.12	TSL:1 MANE Select	c.21G>T	p.Ser7Ser	synonymous	Exon 1 of 9	ENSP00000369857.3	Q6UWZ7-1
	ABRAXAS1	ENST00000515303.2	TSL:1	c.-131G>T		5_prime_UTR	Exon 1 of 3	ENSP00000421068.1	E9PHB9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441456 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 717400

African (AFR) AF: 0.00 AC: 0 AN: 30862

American (AMR) AF: 0.00 AC: 0 AN: 43206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25522

East Asian (EAS) AF: 0.00 AC: 0 AN: 37554

South Asian (SAS) AF: 0.00 AC: 0 AN: 84106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102754

Other (OTH) AF: 0.00 AC: 0 AN: 59396

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.6
DANN	Benign	0.72
PhyloP100		0.27
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs145796091; hg19: chr4-84406205;