12-6638129-G-A

Variant names:

• chr12-6638129-G-A
• rs1045553
• NM_032489.3:c.*153C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032489.3(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 NM_032489.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032489.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACRBP	NM_032489.3	MANE Select	c.*153C>T		3_prime_UTR	Exon 10 of 10	NP_115878.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACRBP	ENST00000229243.7	TSL:1 MANE Select	c.*153C>T		3_prime_UTR	Exon 10 of 10	ENSP00000229243.2
	ACRBP	ENST00000540513.1	TSL:1	n.453C>T		non_coding_transcript_exon	Exon 2 of 2
	ACRBP	ENST00000414226.6	TSL:2	c.*153C>T		downstream_gene	N/A	ENSP00000402725.2

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

African (AFR) AF: 0.464 AC: 9797 AN: 21096

American (AMR) AF: 0.769 AC: 19763 AN: 25696

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 13450 AN: 16942

East Asian (EAS) AF: 0.619 AC: 22337 AN: 36072

South Asian (SAS) AF: 0.721 AC: 42972 AN: 59624

European-Finnish (FIN) AF: 0.804 AC: 32546 AN: 40460

Middle Eastern (MID) AF: 0.789 AC: 2222 AN: 2816

European-Non Finnish (NFE) AF: 0.800 AC: 520702 AN: 650896

Other (OTH) AF: 0.767 AC: 31257 AN: 40742

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

African (AFR) AF: 0.466 AC: 19320 AN: 41428

American (AMR) AF: 0.757 AC: 11560 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2775 AN: 3472

East Asian (EAS) AF: 0.624 AC: 3217 AN: 5156

South Asian (SAS) AF: 0.710 AC: 3420 AN: 4820

European-Finnish (FIN) AF: 0.808 AC: 8555 AN: 10584

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54266 AN: 67996

Other (OTH) AF: 0.735 AC: 1552 AN: 2112

Alfa AF: 0.770 Hom.: 188406

Bravo AF: 0.681

Asia WGS AF: 0.692 AC: 2404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.024
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs1045553; hg19: chr12-6747295;