Variant 8-123966166-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001039112.2(FER1L6):c.260T>A(p.Ile87Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,614,006 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 66 hom. )

Consequence

FER1L6
NM_001039112.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.99

Variant links:

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]

FER1L6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017080188).

BP6

Variant 8-123966166-T-A is Benign according to our data. Variant chr8-123966166-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 789300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FER1L6	NM_001039112.2 link	c.260T>A	p.Ile87Lys	missense_variant	5/41	ENST00000522917.5	NP_001034201.2	Q2WGJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FER1L6	ENST00000522917.5 link	c.260T>A	p.Ile87Lys	missense_variant	5/41	1	NM_001039112.2	ENSP00000428280.1		Q2WGJ9

Frequencies

GnomAD3 genomes

AF:

0.00598

AC:

910

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00415

Gnomad FIN

AF:

0.00924

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00920

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00630

AC:

1568

AN:

249032

Hom.:

AF XY:

0.00665

AC XY:

898

AN XY:

135096

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00458

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00481

Gnomad FIN exome

AF:

0.00933

Gnomad NFE exome

AF:

0.00870

Gnomad OTH exome

AF:

0.00662

GnomAD4 exome

AF:

0.00776

AC:

11339

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00768

AC XY:

5586

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00465

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00441

Gnomad4 FIN exome

AF:

0.00957

Gnomad4 NFE exome

AF:

0.00871

Gnomad4 OTH exome

AF:

0.00745

GnomAD4 genome

AF:

0.00598

AC:

910

AN:

152260

Hom.:

Cov.:

AF XY:

0.00575

AC XY:

428

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00415

Gnomad4 FIN

AF:

0.00924

Gnomad4 NFE

AF:

0.00920

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00753

Hom.:

Bravo

AF:

0.00509

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00119

AC:

ESP6500EA

AF:

0.00780

AC:

ExAC

AF:

0.00615

AC:

745

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00698

EpiControl

AF:

0.00682

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	FER1L6: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.017

MetaSVM

Uncertain

0.098

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.1

REVEL

Pathogenic

0.83

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.97

Vest4

0.90

MVP

0.46

MPC

0.68

ClinPred

0.045

GERP RS

5.3

Varity_R

0.82

gMVP

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over