rs2248178

chr8-102556870-A-Cchr8-102556870-A-T

Variant summary

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

The NM_024410.4(ODF1):c.321-3582A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,194 control chromosomes in the GnomAD database, including 54,344 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 0.84 (54344 hom., cov: 32)
• Consequence: ODF1 NM_024410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

Genes affected

ODF1 (HGNC:8113): (outer dense fiber of sperm tails 1) The outer dense fibers are cytoskeletal structures that surround the axoneme in the middle piece and principal piece of the sperm tail. The fibers function in maintaining the elastic structure and recoil of the sperm tail as well as in protecting the tail from shear forces during epididymal transport and ejaculation. Defects in the outer dense fibers lead to abnormal sperm morphology and infertility. The human outer dense fibers contains at least 10 major proteins and this gene encodes the main protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODF1	NM_024410.4	c.321-3582A>C		intron_variant		ENST00000285402.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODF1	ENST00000285402.4	c.321-3582A>C		intron_variant		1	NM_024410.4	P1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128161 AN: 152076 Hom.: 54310 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.847

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.843 AC: 128253 AN: 152194 Hom.: 54344 Cov.: 32 AF XY: 0.837 AC XY: 62250 AN XY: 74402

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.846

Alfa AF: 0.844 Hom.: 26819

Bravo AF: 0.842

Asia WGS AF: 0.670 AC: 2332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.2
Dann	Benign	0.75

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: rs2248178; hg19: chr8-103569098;