Genetic Variant IZUMO1:c.235+152C>T (chr19-48745473-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_182575.3(IZUMO1):c.235+152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,047,658 control chromosomes in the GnomAD database, including 212,022 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 0.71 ( 40247 hom., cov: 30)

Exomes 𝑓: 0.61 ( 171775 hom. )

Consequence

IZUMO1
NM_182575.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.764

Publications

52 publications found

Variant links:

Genes affected

IZUMO1 (HGNC:28539): (izumo sperm-oocyte fusion 1) The sperm-specific protein Izumo, named for a Japanese shrine dedicated to marriage, is essential for sperm-egg plasma membrane binding and fusion (Inoue et al., 2005 [PubMed 15759005]).[supplied by OMIM, Mar 2008]

IZUMO1 links:

Genome browser will be placed here

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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182575.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IZUMO1	NM_182575.3	MANE Select	c.235+152C>T	intron	N/A	NP_872381.2
IZUMO1	NM_001321864.1		c.-104-185C>T	intron	N/A	NP_001308793.1
IZUMO1	NM_001321865.1		c.-325+152C>T	intron	N/A	NP_001308794.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IZUMO1	ENST00000332955.7	TSL:1 MANE Select	c.235+152C>T	intron	N/A	ENSP00000327786.2
IZUMO1	ENST00000595517.5	TSL:1	n.169-185C>T	intron	N/A	ENSP00000471815.1
IZUMO1	ENST00000595937.5	TSL:1	n.235+152C>T	intron	N/A	ENSP00000470144.1

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107622

AN:

151858

Hom.:

40175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.918

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.713

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.763

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.666

GnomAD4 exome

AF:

0.605

AC:

542298

AN:

895680

Hom.:

171775

Cov.:

AF XY:

0.610

AC XY:

277638

AN XY:

455268

show subpopulations

African (AFR)

AF:

0.930

AC:

19417

AN:

20868

American (AMR)

AF:

0.760

AC:

19735

AN:

25982

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

10470

AN:

18292

East Asian (EAS)

AF:

0.998

AC:

34519

AN:

34604

South Asian (SAS)

AF:

0.733

AC:

44552

AN:

60796

European-Finnish (FIN)

AF:

0.657

AC:

29180

AN:

44382

Middle Eastern (MID)

AF:

0.547

AC:

2422

AN:

4426

European-Non Finnish (NFE)

AF:

0.553

AC:

356826

AN:

645444

Other (OTH)

AF:

0.616

AC:

25177

AN:

40886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

11080

22161

33241

44322

55402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8104

16208

24312

32416

40520

<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:

0.709

AC:

107765

AN:

151978

Hom.:

40247

Cov.:

AF XY:

0.716

AC XY:

53160

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.918

AC:

38110

AN:

41498

American (AMR)

AF:

0.714

AC:

10883

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

2005

AN:

3462

East Asian (EAS)

AF:

0.997

AC:

5148

AN:

5164

South Asian (SAS)

AF:

0.763

AC:

3669

AN:

4808

European-Finnish (FIN)

AF:

0.660

AC:

6967

AN:

10562

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.570

AC:

38747

AN:

67928

Other (OTH)

AF:

0.671

AC:

1414

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1394

2788

4182

5576

6970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<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:

0.647

Hom.:

50871

Bravo

AF:

0.721

Asia WGS

AF:

0.902

AC:

3135

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.095

(source)

DANN

Benign

0.81

PhyloP100

-0.76

Mutation Taster

=100/0

polymorphism (auto)

(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

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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