Variant rs6009961 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001097.3(ACR):c.566-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,482,114 control chromosomes in the GnomAD database, including 387,615 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41958 hom., cov: 26)

Exomes 𝑓: 0.70 ( 345657 hom. )

Consequence

ACR
NM_001097.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001893

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.377

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 22-50744057-A-G is Benign according to our data. Variant chr22-50744057-A-G is described in ClinVar as [Benign]. Clinvar id is 402335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACR	NM_001097.3 linkuse as main transcript	c.566-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000216139.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACR	ENST00000216139.10 linkuse as main transcript	c.566-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001097.3	P1

Frequencies

GnomAD3 genomes

AF:

0.737

AC:

111259

AN:

150872

Hom.:

41911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.877

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.662

Gnomad ASJ

AF:

0.717

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.531

Gnomad FIN

AF:

0.702

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.716

Gnomad OTH

AF:

0.736

GnomAD3 exomes

AF:

0.657

AC:

161125

AN:

245076

Hom.:

54934

AF XY:

0.653

AC XY:

86473

AN XY:

132516

show subpopulations

Gnomad AFR exome

AF:

0.888

Gnomad AMR exome

AF:

0.561

Gnomad ASJ exome

AF:

0.702

Gnomad EAS exome

AF:

0.411

Gnomad SAS exome

AF:

0.538

Gnomad FIN exome

AF:

0.699

Gnomad NFE exome

AF:

0.713

Gnomad OTH exome

AF:

0.667

GnomAD4 exome

AF:

0.705

AC:

938035

AN:

1331128

Hom.:

345657

Cov.:

AF XY:

0.699

AC XY:

465895

AN XY:

666922

show subpopulations

Gnomad4 AFR exome

AF:

0.893

Gnomad4 AMR exome

AF:

0.579

Gnomad4 ASJ exome

AF:

0.702

Gnomad4 EAS exome

AF:

0.396

Gnomad4 SAS exome

AF:

0.541

Gnomad4 FIN exome

AF:

0.711

Gnomad4 NFE exome

AF:

0.731

Gnomad4 OTH exome

AF:

0.705

GnomAD4 genome

AF:

0.738

AC:

111370

AN:

150986

Hom.:

41958

Cov.:

AF XY:

0.728

AC XY:

53684

AN XY:

73694

show subpopulations

Gnomad4 AFR

AF:

0.877

Gnomad4 AMR

AF:

0.662

Gnomad4 ASJ

AF:

0.717

Gnomad4 EAS

AF:

0.420

Gnomad4 SAS

AF:

0.531

Gnomad4 FIN

AF:

0.702

Gnomad4 NFE

AF:

0.715

Gnomad4 OTH

AF:

0.739

Alfa

AF:

0.724

Hom.:

8417

Bravo

AF:

0.739

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 66% of total chromosomes in ExAC -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.1

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.022

SpliceAI score (max)

0.080

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