5-35799892-A-G

Position:

• chr5-35799892-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024867.4(SPEF2):​c.4831-76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,508,870 control chromosomes in the GnomAD database, including 381,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (38516 hom., cov: 31)
  • Exomes 𝑓: 0.71 (343192 hom.)
• Consequence: SPEF2 NM_024867.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0460

Genes affected

SPEF2 (HGNC:26293): (sperm flagellar 2) Involved in sperm axoneme assembly. Located in sperm flagellum. Implicated in spermatogenic failure 43. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 5-35799892-A-G is Benign according to our data. Variant chr5-35799892-A-G is described in ClinVar as [Benign]. Clinvar id is 1244371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPEF2	NM_024867.4	c.4831-76A>G		intron_variant		ENST00000356031.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPEF2	ENST00000356031.8	c.4831-76A>G		intron_variant		1	NM_024867.4	P2
	ENST00000510433.1	n.173+26954T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107684 AN: 151846 Hom.: 38463 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.682

GnomAD4 exome AF: 0.709 AC: 962556 AN: 1356906 Hom.: 343192 AF XY: 0.712 AC XY: 478955 AN XY: 673150

Gnomad4 AFR exome AF: 0.703

Gnomad4 AMR exome AF: 0.752

Gnomad4 ASJ exome AF: 0.653

Gnomad4 EAS exome AF: 0.843

Gnomad4 SAS exome AF: 0.813

Gnomad4 FIN exome AF: 0.723

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.709 AC: 107796 AN: 151964 Hom.: 38516 Cov.: 31 AF XY: 0.713 AC XY: 52962 AN XY: 74270

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.687

Alfa AF: 0.694 Hom.: 65194

Bravo AF: 0.705

Asia WGS AF: 0.829 AC: 2884 AN: 3478

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

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.7
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: rs3822735; hg19: chr5-35799994;