rs838145

chr19-48745473-G-Achr19-48745473-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
IZUMO1	NM_182575.3	c.235+152C>T		intron_variant		ENST00000332955.7
IZUMO1	NM_001321864.1	c.-104-185C>T		intron_variant
IZUMO1	NM_001321865.1	c.-325+152C>T		intron_variant
IZUMO1	NR_135832.1	n.242-185C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IZUMO1	ENST00000332955.7	c.235+152C>T		intron_variant		1	NM_182575.3	P1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107622 AN: 151858 Hom.: 40175 Cov.: 30

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.: 12 AF XY: 0.610 AC XY: 277638 AN XY: 455268

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.: 30 AF XY: 0.716 AC XY: 53160 AN XY: 74258

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

Other links and lift over

dbSNP: rs838145; hg19: chr19-49248730;