rs2285395

Positions:

• chr22-50739662-G-A

Variant summary

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

The NM_001097.3(ACR):​c.282-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 1,537,440 control chromosomes in the GnomAD database, including 2,721 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 0.073 (478 hom., cov: 32)
  • Exomes 𝑓: 0.053 (2243 hom.)
• Consequence: ACR NM_001097.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

Genes affected

ACR (HGNC:126): (acrosin) Acrosin is the major proteinase present in the acrosome of mature spermatozoa. It is a typical serine proteinase with trypsin-like specificity. It is stored in the acrosome in its precursor form, proacrosin. The active enzyme functions in the lysis of the zona pellucida, thus facilitating penetration of the sperm through the innermost glycoprotein layers of the ovum. The mRNA for proacrosin is synthesized only in the postmeiotic stages of spermatogenesis. In humans proacrosin first appears in the haploid spermatids. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACR	NM_001097.3	c.282-32G>A		intron_variant		ENST00000216139.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACR	ENST00000216139.10	c.282-32G>A		intron_variant		1	NM_001097.3	P1
ACR	ENST00000533930.1	n.322-32G>A		intron_variant, non_coding_transcript_variant		1
ACR	ENST00000529621.1	c.282-32G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11140 AN: 152146 Hom.: 472 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.0724

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0549

GnomAD3 exomes AF: 0.0536 AC: 10110 AN: 188654 Hom.: 346 AF XY: 0.0519 AC XY: 5183 AN XY: 99842

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.0236

Gnomad ASJ exome AF: 0.0277

Gnomad EAS exome AF: 0.0364

Gnomad SAS exome AF: 0.0495

Gnomad FIN exome AF: 0.0715

Gnomad NFE exome AF: 0.0514

Gnomad OTH exome AF: 0.0517

GnomAD4 exome AF: 0.0532 AC: 73713 AN: 1385176 Hom.: 2243 Cov.: 31 AF XY: 0.0527 AC XY: 35864 AN XY: 680716

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.0257

Gnomad4 ASJ exome AF: 0.0252

Gnomad4 EAS exome AF: 0.0224

Gnomad4 SAS exome AF: 0.0455

Gnomad4 FIN exome AF: 0.0705

Gnomad4 NFE exome AF: 0.0536

Gnomad4 OTH exome AF: 0.0527

GnomAD4 genome AF: 0.0733 AC: 11163 AN: 152264 Hom.: 478 Cov.: 32 AF XY: 0.0740 AC XY: 5510 AN XY: 74466

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0420

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.0363

Gnomad4 SAS AF: 0.0460

Gnomad4 FIN AF: 0.0724

Gnomad4 NFE AF: 0.0551

Gnomad4 OTH AF: 0.0619

Alfa AF: 0.0527 Hom.: 385

Bravo AF: 0.0724

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0070
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2285395; hg19: chr22-51178090;