14-60490561-C-T

Variant names:

• chr14-60490561-C-T
• rs2093210
• ENST00000556799.1:c.-8-5475G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000556799.1(C14orf39):​c.-8-5475G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,894 control chromosomes in the GnomAD database, including 19,436 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 0.45 (19436 hom., cov: 31)
• Consequence: C14orf39 ENST00000556799.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 47 publications found

Genes affected

C14orf39 (HGNC:19849): (chromosome 14 open reading frame 39) Predicted to be involved in gamete generation and meiosis I. Predicted to be located in chromosome. Predicted to be active in central element. Implicated in primary ovarian insufficiency 18 and spermatogenic failure 52. [provided by Alliance of Genome Resources, Apr 2022]

C14orf39 Gene-Disease associations (from GenCC):

• premature ovarian failure 18

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• spermatogenic failure 52

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C14orf39	XM_047431324.1	c.-8-5475G>A		intron_variant	Intron 2 of 18		XP_047287280.1
C14orf39	XM_017021250.3	c.-5+8735G>A		intron_variant	Intron 1 of 13		XP_016876739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C14orf39	ENST00000556799.1	c.-8-5475G>A		intron_variant	Intron 2 of 5	4		ENSP00000451441.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68536 AN: 151778 Hom.: 19429 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.451 AC: 68561 AN: 151894 Hom.: 19436 Cov.: 31 AF XY: 0.457 AC XY: 33942 AN XY: 74236

African (AFR) AF: 0.114 AC: 4736 AN: 41444

American (AMR) AF: 0.592 AC: 9039 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1754 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1195 AN: 5168

South Asian (SAS) AF: 0.420 AC: 2016 AN: 4800

European-Finnish (FIN) AF: 0.724 AC: 7603 AN: 10502

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40709 AN: 67938

Other (OTH) AF: 0.426 AC: 896 AN: 2102

Alfa AF: 0.513 Hom.: 2999

Bravo AF: 0.428

Asia WGS AF: 0.321 AC: 1117 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.66
PhyloP100		0.30

Splicing

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

Other links and lift over

dbSNP: rs2093210; hg19: chr14-60957279;