rs1116853

Variant names:

• chr14-60450758-G-A
• rs1116853
• NM_174978.3:c.1503+4243C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-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 rank	MANE	Protein	UniProt
C14orf39	NM_174978.3	c.1503+4243C>T		intron_variant	Intron 16 of 17	ENST00000321731.8	NP_777638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C14orf39	ENST00000321731.8	c.1503+4243C>T		intron_variant	Intron 16 of 17	1	NM_174978.3	ENSP00000324920.3
C14orf39	ENST00000557138.5	n.*817+4243C>T		intron_variant	Intron 11 of 12	1		ENSP00000450476.1
C14orf39	ENST00000498565.5	n.48+4243C>T		intron_variant	Intron 1 of 4	3		ENSP00000451937.1

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

African (AFR) AF: 0.235 AC: 9744 AN: 41470

American (AMR) AF: 0.0936 AC: 1431 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3470

East Asian (EAS) AF: 0.124 AC: 640 AN: 5156

South Asian (SAS) AF: 0.262 AC: 1263 AN: 4814

European-Finnish (FIN) AF: 0.0256 AC: 272 AN: 10612

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5418 AN: 68006

Other (OTH) AF: 0.128 AC: 271 AN: 2112

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
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1116853; hg19: chr14-60917476;