22-50738236-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PVS1_SupportingBP6_ModerateBS1BS2

The NM_001097.3(ACR):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 1,613,968 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 5 hom. )

Consequence

ACR
NM_001097.3 start_lost

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.150

Publications

2 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:

ENSG00000225929 (HGNC:):

ENSG00000225929 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 4 codons. Genomic position: 50738245. Lost 0.008 part of the original CDS.

BP6

Variant 22-50738236-A-G is Benign according to our data. Variant chr22-50738236-A-G is described in ClinVar as Benign. ClinVar VariationId is 731265.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000723 (110/152236) while in subpopulation EAS AF = 0.018 (93/5176). AF 95% confidence interval is 0.015. There are 1 homozygotes in GnomAd4. There are 58 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

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.1A>G	p.Met1?	start_lost	Exon 1 of 5	NP_001088.2	P10323
	LOC105373100	NR_134637.1		n.-67T>C		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACR	ENST00000216139.10	TSL:1 MANE Select	c.1A>G	p.Met1?	start_lost	Exon 1 of 5	ENSP00000216139.5	P10323
ACR	ENST00000533930.1	TSL:1	n.41A>G		non_coding_transcript_exon	Exon 1 of 3
ACR	ENST00000529621.1	TSL:5	c.1A>G	p.Met1?	start_lost	Exon 1 of 4	ENSP00000435120.1	E9PLV5

Frequencies

GnomAD3 genomes

AF:

0.000710

AC:

108

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0179

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00165

AC:

415

AN:

251348

AF XY:

0.00149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0219

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000521

AC:

761

AN:

1461732

Hom.:

Cov.:

AF XY:

0.000517

AC XY:

376

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000671

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0161

AC:

640

AN:

39700

South Asian (SAS)

AF:

0.000475

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111904

Other (OTH)

AF:

0.00116

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

130

173

216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000723

AC:

110

AN:

152236

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41552

American (AMR)

AF:

0.000131

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0180

AC:

AN:

5176

South Asian (SAS)

AF:

0.00124

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67986

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000925

Hom.:

Bravo

AF:

0.000831

ExAC

AF:

0.00168

AC:

204

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

4.5

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.24

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.10

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.77

PhyloP100

-0.15

PROVEAN

Benign

-0.60

REVEL

Benign

0.24

Sift

Uncertain

0.011

Sift4G

Uncertain

0.019

Polyphen

0.0010

Vest4

0.35

MVP

0.87

ClinPred

0.023

GERP RS

-2.2

PromoterAI

0.046

Neutral

(source)

Varity_R

0.21

gMVP

0.48

Mutation Taster

=189/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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