rs2277862

Positions:

• chr20-35564866-C-T

Variant summary

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

The NR_119376.1(FER1L4):​n.4574G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 455,700 control chromosomes in the GnomAD database, including 7,891 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 0.17 (2350 hom., cov: 32)
  • Exomes 𝑓: 0.18 (5541 hom.)
• Consequence: FER1L4 NR_119376.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275

Genes affected

FER1L4 (HGNC:15801): (fer-1 like family member 4 (pseudogene)) Predicted to enable metal ion binding activity. Predicted to be involved in plasma membrane organization. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FER1L4	NR_119376.1	n.4574G>A		non_coding_transcript_exon_variant	37/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FER1L4	ENST00000615531.4	n.4562G>A		non_coding_transcript_exon_variant	37/45

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25435 AN: 152060 Hom.: 2350 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.187

GnomAD3 exomes AF: 0.184 AC: 25685 AN: 139410 Hom.: 2626 AF XY: 0.190 AC XY: 14341 AN XY: 75570

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.141

Gnomad SAS exome AF: 0.277

Gnomad FIN exome AF: 0.0836

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.179 AC: 54474 AN: 303522 Hom.: 5541 Cov.: 0 AF XY: 0.189 AC XY: 32751 AN XY: 172892

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.0891

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.167 AC: 25447 AN: 152178 Hom.: 2350 Cov.: 32 AF XY: 0.167 AC XY: 12420 AN XY: 74406

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.0906

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.187

Alfa AF: 0.158 Hom.: 4230

Bravo AF: 0.172

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.6
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277862; hg19: chr20-34152782; COSMIC: COSV53413602;