19-48743609-A-G

Variant names:

• chr19-48743609-A-G
• rs838147
• NM_182575.3:c.419-84T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 43 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IZUMO1	NM_182575.3	MANE Select	c.419-84T>C		intron	N/A	NP_872381.2
	IZUMO1	NM_001321864.1		c.80-84T>C		intron	N/A	NP_001308793.1
	IZUMO1	NM_001321865.1		c.-141-84T>C		intron	N/A	NP_001308794.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IZUMO1	ENST00000332955.7	TSL:1 MANE Select	c.419-84T>C		intron	N/A	ENSP00000327786.2
	IZUMO1	ENST00000595517.5	TSL:1	n.*145-84T>C		intron	N/A	ENSP00000471815.1
	IZUMO1	ENST00000595937.5	TSL:1	n.419-84T>C		intron	N/A	ENSP00000470144.1

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

African (AFR) AF: 0.721 AC: 16026 AN: 22240

American (AMR) AF: 0.740 AC: 29025 AN: 39238

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 11687 AN: 22212

East Asian (EAS) AF: 0.990 AC: 35776 AN: 36130

South Asian (SAS) AF: 0.718 AC: 52362 AN: 72880

European-Finnish (FIN) AF: 0.588 AC: 29847 AN: 50778

Middle Eastern (MID) AF: 0.506 AC: 2367 AN: 4678

European-Non Finnish (NFE) AF: 0.517 AC: 309356 AN: 598412

Other (OTH) AF: 0.573 AC: 23690 AN: 41374

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

African (AFR) AF: 0.709 AC: 29430 AN: 41504

American (AMR) AF: 0.656 AC: 10017 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1820 AN: 3468

East Asian (EAS) AF: 0.994 AC: 5141 AN: 5174

South Asian (SAS) AF: 0.747 AC: 3604 AN: 4822

European-Finnish (FIN) AF: 0.592 AC: 6271 AN: 10586

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35495 AN: 67968

Other (OTH) AF: 0.591 AC: 1248 AN: 2112

Alfa AF: 0.624 Hom.: 13259

Bravo AF: 0.625

Asia WGS AF: 0.881 AC: 3060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs838147; hg19: chr19-49246866;