chr14-22995273-G-A

Variant names:

• chr14-22995273-G-A
• rs997154
• NM_021944.4:c.918+675C>T

Variant summary

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

The NM_021944.4(C14orf93):​c.918+675C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,154 control chromosomes in the GnomAD database, including 3,829 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 0.22 (3829 hom., cov: 31)
• Consequence: C14orf93 NM_021944.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 20 publications found

Genes affected

C14orf93 (HGNC:20162): (chromosome 14 open reading frame 93) Enables RNA binding activity. Predicted to act upstream of or within anatomical structure development; cell differentiation; and positive regulation of gene expression. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

AJUBA-DT (HGNC:55449): (AJUBA divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021944.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C14orf93	NM_021944.4	MANE Select	c.918+675C>T		intron	N/A	NP_068763.2
	C14orf93	NM_001130706.3		c.918+675C>T		intron	N/A	NP_001124178.1
	C14orf93	NM_001130708.3		c.918+675C>T		intron	N/A	NP_001124180.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C14orf93	ENST00000299088.11	TSL:2 MANE Select	c.918+675C>T		intron	N/A	ENSP00000299088.6
	C14orf93	ENST00000397379.7	TSL:1	c.918+675C>T		intron	N/A	ENSP00000380535.3
	C14orf93	ENST00000341470.8	TSL:1	c.918+675C>T		intron	N/A	ENSP00000341353.4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33600 AN: 152036 Hom.: 3817 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.221 AC: 33637 AN: 152154 Hom.: 3829 Cov.: 31 AF XY: 0.220 AC XY: 16335 AN XY: 74370

African (AFR) AF: 0.232 AC: 9644 AN: 41492

American (AMR) AF: 0.197 AC: 3013 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3472

East Asian (EAS) AF: 0.0462 AC: 240 AN: 5194

South Asian (SAS) AF: 0.161 AC: 777 AN: 4826

European-Finnish (FIN) AF: 0.282 AC: 2982 AN: 10576

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.228 AC: 15486 AN: 68002

Other (OTH) AF: 0.225 AC: 475 AN: 2110

Alfa AF: 0.220 Hom.: 7159

Bravo AF: 0.215

Asia WGS AF: 0.161 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.51
PhyloP100		0.088
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: rs997154; hg19: chr14-23464482;