dbSNP rs838145: IZUMO1:c.235+152C>T (chr19-48745473-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IZUMO1	NM_182575.3 link	c.235+152C>T	intron_variant	Intron 2 of 9	ENST00000332955.7	NP_872381.2	Q8IYV9-1
IZUMO1	NM_001321864.1 link	c.-104-185C>T	intron_variant	Intron 1 of 8		NP_001308793.1
IZUMO1	NM_001321865.1 link	c.-325+152C>T	intron_variant	Intron 1 of 8		NP_001308794.1	Q8IYV9
IZUMO1	NR_135832.1 link	n.242-185C>T	intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IZUMO1	ENST00000332955.7 link	c.235+152C>T		intron_variant	Intron 2 of 9	1	NM_182575.3	ENSP00000327786.2		Q8IYV9-1

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

Gnomad4 AFR exome

AF:

0.930

Gnomad4 AMR exome

AF:

0.760

Gnomad4 ASJ exome

AF:

0.572

Gnomad4 EAS exome

AF:

0.998

Gnomad4 SAS exome

AF:

0.733

Gnomad4 FIN exome

AF:

0.657

Gnomad4 NFE exome

AF:

0.553

Gnomad4 OTH exome

AF:

0.616

GnomAD4 genome

AF:

0.709

AC:

107765

AN:

151978

Hom.:

40247

Cov.:

AF XY:

0.716

AC XY:

53160

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.918

Gnomad4 AMR

AF:

0.714

Gnomad4 ASJ

AF:

0.579

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.763

Gnomad4 FIN

AF:

0.660

Gnomad4 NFE

AF:

0.570

Gnomad4 OTH

AF:

0.671

Alfa

AF:

0.683

Hom.:

6512

Bravo

AF:

0.721

Asia WGS

AF:

0.902

AC:

3135

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.095

DANN

Benign

0.81

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over