Variant chr22-50738236-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 8P and 10B. PVS1BP6_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

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

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BP6

Variant 22-50738236-A-G is Benign according to our data. Variant chr22-50738236-A-G is described in ClinVar as [Benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACR	NM_001097.3 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/5	ENST00000216139.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ACR	ENST00000216139.10 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/5	1	NM_001097.3	P1
ACR	ENST00000533930.1 linkuse as main transcript	n.41A>G		non_coding_transcript_exon_variant	1/3	1
ACR	ENST00000529621.1 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/4	5

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

GnomAD3 exomes

AF:

0.00165

AC:

415

AN:

251348

Hom.:

AF XY:

0.00149

AC XY:

202

AN XY:

135848

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 SAS exome

AF:

0.000229

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0161

Gnomad4 SAS exome

AF:

0.000475

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.000723

AC:

110

AN:

152236

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0180

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00106

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

4.5

DANN

Benign

0.64

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.10

MetaRNN

Benign

0.0096

T;T

MetaSVM

Benign

-0.77

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.60

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.0010

B;B

Vest4

0.35

MVP

0.87

ClinPred

0.023

GERP RS

-2.2

Varity_R

0.21

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over