rs1116853

Positions:

• chr14-60450758-G-A

Variant summary

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

The NM_174978.3(C14orf39):​c.1503+4243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,132 control chromosomes in the GnomAD database, including 1,740 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 0.13 (1740 hom., cov: 32)
• Consequence: C14orf39 NM_174978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C14orf39	NM_174978.3	c.1503+4243C>T		intron_variant		ENST00000321731.8	NP_777638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C14orf39	ENST00000321731.8	c.1503+4243C>T		intron_variant		1	NM_174978.3	ENSP00000324920	P1
C14orf39	ENST00000557138.5	c.*817+4243C>T		intron_variant, NMD_transcript_variant		1		ENSP00000450476
C14orf39	ENST00000498565.5	c.50+4243C>T		intron_variant, NMD_transcript_variant		3		ENSP00000451937

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19482 AN: 152014 Hom.: 1746 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.0939

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.128 AC: 19477 AN: 152132 Hom.: 1740 Cov.: 32 AF XY: 0.126 AC XY: 9404 AN XY: 74370

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.0256

Gnomad4 NFE AF: 0.0797

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0962 Hom.: 168

Bravo AF: 0.135

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.46
DANN	Benign	0.33

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: rs1116853; hg19: chr14-60917476;