8-123852164-G-A

Position:

• chr8-123852164-G-A

Variant summary

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

The NM_001039112.2(FER1L6):​c.-29G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,134 control chromosomes in the GnomAD database, including 12,529 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 0.39 (12524 hom., cov: 32)
  • Exomes 𝑓: 0.55 (5 hom.)
• Consequence: FER1L6 NM_001039112.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594

Genes affected

FER1L6 (HGNC:28065): (fer-1 like family member 6) Predicted to enable metal ion binding activity. Predicted to be involved in plasma membrane organization. Predicted to act upstream of or within response to bacterium. Predicted to be integral component of membrane. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FER1L6	NM_001039112.2	c.-29G>A		5_prime_UTR_premature_start_codon_gain_variant	1/41	ENST00000522917.5	NP_001034201.2
FER1L6	NM_001039112.2	c.-29G>A		5_prime_UTR_variant	1/41	ENST00000522917.5	NP_001034201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FER1L6	ENST00000522917	c.-29G>A		5_prime_UTR_premature_start_codon_gain_variant	1/41	1	NM_001039112.2	ENSP00000428280.1
FER1L6	ENST00000522917	c.-29G>A		5_prime_UTR_variant	1/41	1	NM_001039112.2	ENSP00000428280.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59895 AN: 151974 Hom.: 12525 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.548 AC: 23 AN: 42 Hom.: 5 Cov.: 0 AF XY: 0.563 AC XY: 18 AN XY: 32

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.611

GnomAD4 genome AF: 0.394 AC: 59903 AN: 152092 Hom.: 12524 Cov.: 32 AF XY: 0.388 AC XY: 28813 AN XY: 74350

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.391

Alfa AF: 0.435 Hom.: 19005

Bravo AF: 0.381

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1897318; hg19: chr8-124864404;