rs1045553

Positions:

• chr12-6638129-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000229243.7(ACRBP):​c.*153C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,046,392 control chromosomes in the GnomAD database, including 310,480 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (38281 hom., cov: 32)
  • Exomes 𝑓: 0.78 (272199 hom.)
• Consequence: ACRBP ENST00000229243.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

Genes affected

ACRBP (HGNC:17195): (acrosin binding protein) The protein encoded by this gene is similar to proacrosin binding protein sp32 precursor found in mouse, guinea pig, and pig. This protein is located in the sperm acrosome and is thought to function as a binding protein to proacrosin for packaging and condensation of the acrosin zymogen in the acrosomal matrix. This protein is a member of the cancer/testis family of antigens and it is found to be immunogenic. In normal tissues, this mRNA is expressed only in testis, whereas it is detected in a range of different tumor types such as bladder, breast, lung, liver, and colon. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACRBP	NM_032489.3	c.*153C>T		3_prime_UTR_variant	10/10	ENST00000229243.7	NP_115878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACRBP	ENST00000229243.7	c.*153C>T		3_prime_UTR_variant	10/10	1	NM_032489.3	ENSP00000229243	P1
ACRBP	ENST00000540513.1	n.453C>T		non_coding_transcript_exon_variant	2/2	1
ACRBP	ENST00000414226.6			downstream_gene_variant		2		ENSP00000402725

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105496 AN: 151930 Hom.: 38280 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.735

GnomAD4 exome AF: 0.777 AC: 695046 AN: 894344 Hom.: 272199 Cov.: 12 AF XY: 0.776 AC XY: 351590 AN XY: 452822

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.769

Gnomad4 ASJ exome AF: 0.794

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.721

Gnomad4 FIN exome AF: 0.804

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.694 AC: 105532 AN: 152048 Hom.: 38281 Cov.: 32 AF XY: 0.694 AC XY: 51600 AN XY: 74334

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.735

Alfa AF: 0.783 Hom.: 93308

Bravo AF: 0.681

Asia WGS AF: 0.692 AC: 2404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

LitVar

Other links and lift over

dbSNP: rs1045553; hg19: chr12-6747295;