chr8-102560804-AACCCGTGCAG-A

Position:

• chr8-102560804-AACCCGTGCAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024410.4(ODF1):​c.674_683delACCCGTGCAG​(p.Asn225fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 897,406 control chromosomes in the GnomAD database, including 2,744 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1473 hom., cov: 0)
  • Exomes 𝑓: 0.017 (1271 hom.)
• Consequence: ODF1 NM_024410.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.65

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 -10 ACMG points.

• BP6: Variant 8-102560804-AACCCGTGCAG-A is Benign according to our data. Variant chr8-102560804-AACCCGTGCAG-A is described in ClinVar as [Benign]. Clinvar id is 776369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF1	NM_024410.4	c.674_683delACCCGTGCAG	p.Asn225fs	frameshift_variant	2/2	ENST00000285402.4	NP_077721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF1	ENST00000285402.4	c.674_683delACCCGTGCAG	p.Asn225fs	frameshift_variant	2/2	1	NM_024410.4	ENSP00000285402.3
ODF1	ENST00000518835.1	c.53_62delACCCGTGCAG	p.Asn18fs	frameshift_variant	2/2	3		ENSP00000430023.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 11908 AN: 105360 Hom.: 1462 Cov.: 0

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0547

Gnomad ASJ AF: 0.00309

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.00277

Gnomad FIN AF: 0.00192

Gnomad MID AF: 0.0442

Gnomad NFE AF: 0.00726

Gnomad OTH AF: 0.0839

GnomAD4 exome AF: 0.0165 AC: 13087 AN: 791920 Hom.: 1271 AF XY: 0.0148 AC XY: 5820 AN XY: 391934

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.0397

Gnomad4 ASJ exome AF: 0.00448

Gnomad4 EAS exome AF: 0.0298

Gnomad4 SAS exome AF: 0.00410

Gnomad4 FIN exome AF: 0.00246

Gnomad4 NFE exome AF: 0.00474

Gnomad4 OTH exome AF: 0.0335

GnomAD4 genome AF: 0.113 AC: 11962 AN: 105486 Hom.: 1473 Cov.: 0 AF XY: 0.109 AC XY: 5613 AN XY: 51282

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.00309

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.00278

Gnomad4 FIN AF: 0.00192

Gnomad4 NFE AF: 0.00727

Gnomad4 OTH AF: 0.0828

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 20, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs751927082; hg19: chr8-103573032; COSMIC: COSV53433134;