19-48743609-A-G

Position:

• chr19-48743609-A-G

Variant summary

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

The NM_182575.3(IZUMO1):​c.419-84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,040,056 control chromosomes in the GnomAD database, including 184,043 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 0.62 (30045 hom., cov: 32)
  • Exomes 𝑓: 0.57 (153998 hom.)
• Consequence: IZUMO1 NM_182575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IZUMO1	NM_182575.3	c.419-84T>C		intron_variant		ENST00000332955.7	NP_872381.2
IZUMO1	NM_001321864.1	c.80-84T>C		intron_variant			NP_001308793.1
IZUMO1	NM_001321865.1	c.-141-84T>C		intron_variant			NP_001308794.1
IZUMO1	NR_135832.1	n.425-84T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IZUMO1	ENST00000332955.7	c.419-84T>C		intron_variant		1	NM_182575.3	ENSP00000327786.2
IZUMO1	ENST00000595517.5	n.*145-84T>C		intron_variant		1		ENSP00000471815.1
IZUMO1	ENST00000595937.5	n.419-84T>C		intron_variant		1		ENSP00000470144.1
IZUMO1	ENST00000597553.1	n.1641T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93658 AN: 151996 Hom.: 29994 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.585

GnomAD4 exome AF: 0.575 AC: 510136 AN: 887942 Hom.: 153998 Cov.: 12 AF XY: 0.578 AC XY: 267252 AN XY: 462488

Gnomad4 AFR exome AF: 0.721

Gnomad4 AMR exome AF: 0.740

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.990

Gnomad4 SAS exome AF: 0.718

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.573

GnomAD4 genome AF: 0.616 AC: 93773 AN: 152114 Hom.: 30045 Cov.: 32 AF XY: 0.624 AC XY: 46431 AN XY: 74356

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.591

Alfa AF: 0.566 Hom.: 4022

Bravo AF: 0.625

Asia WGS AF: 0.881 AC: 3060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.67

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: rs838147; hg19: chr19-49246866;