dbSNP rs2285395: ACR:c.282-32G>A (chr22-50739662-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54

Publications

19 publications found

Variant links:

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]

ACR links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001097.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001097.3. 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
	ACR	NM_001097.3	MANE Select	c.282-32G>A		intron	N/A	NP_001088.2	P10323

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACR	ENST00000216139.10	TSL:1 MANE Select	c.282-32G>A	intron	N/A	ENSP00000216139.5	P10323
ACR	ENST00000533930.1	TSL:1	n.322-32G>A	intron	N/A
ACR	ENST00000529621.1	TSL:5	c.282-32G>A	intron	N/A	ENSP00000435120.1	E9PLV5

Frequencies

GnomAD3 genomes

AF:

0.0732

AC:

11140

AN:

152146

Hom.:

472

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0536

AC:

10110

AN:

188654

AF XY:

0.0519

show subpopulations

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 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.:

AF XY:

0.0527

AC XY:

35864

AN XY:

680716

show subpopulations

African (AFR)

AF:

0.128

AC:

3999

AN:

31162

American (AMR)

AF:

0.0257

AC:

883

AN:

34368

Ashkenazi Jewish (ASJ)

AF:

0.0252

AC:

529

AN:

20992

East Asian (EAS)

AF:

0.0224

AC:

876

AN:

39124

South Asian (SAS)

AF:

0.0455

AC:

3345

AN:

73438

European-Finnish (FIN)

AF:

0.0705

AC:

3433

AN:

48678

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

5372

European-Non Finnish (NFE)

AF:

0.0536

AC:

57584

AN:

1075046

Other (OTH)

AF:

0.0527

AC:

3005

AN:

56996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

3449

6899

10348

13798

17247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2226

4452

6678

8904

11130

<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:

0.0733

AC:

11163

AN:

152264

Hom.:

478

Cov.:

AF XY:

0.0740

AC XY:

5510

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.127

AC:

5288

AN:

41546

American (AMR)

AF:

0.0420

AC:

643

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

AN:

3468

East Asian (EAS)

AF:

0.0363

AC:

188

AN:

5184

South Asian (SAS)

AF:

0.0460

AC:

222

AN:

4822

European-Finnish (FIN)

AF:

0.0724

AC:

768

AN:

10604

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0551

AC:

3748

AN:

68024

Other (OTH)

AF:

0.0619

AC:

131

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

529

1059

1588

2118

2647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0548

Hom.:

524

Bravo

AF:

0.0724

Asia WGS

AF:

0.0870

AC:

303

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.0070

(source)

DANN

Benign

0.51

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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