Variant 8-123975164-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001039112.2(FER1L6):c.541A>G(p.Asn181Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,604,622 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 38 hom., cov: 30)

Exomes 𝑓: 0.0013 ( 34 hom. )

Consequence

FER1L6
NM_001039112.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.60

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031511784).

BP6

Variant 8-123975164-A-G is Benign according to our data. Variant chr8-123975164-A-G is described in ClinVar as [Benign]. Clinvar id is 713507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1969/152204) while in subpopulation AFR AF= 0.0454 (1885/41516). AF 95% confidence interval is 0.0437. There are 38 homozygotes in gnomad4. There are 943 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FER1L6	NM_001039112.2 link	c.541A>G	p.Asn181Asp	missense_variant	8/41	ENST00000522917.5	NP_001034201.2	Q2WGJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FER1L6	ENST00000522917.5 link	c.541A>G	p.Asn181Asp	missense_variant	8/41	1	NM_001039112.2	ENSP00000428280.1		Q2WGJ9

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1958

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0452

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00329

AC:

803

AN:

243754

Hom.:

AF XY:

0.00244

AC XY:

322

AN XY:

132180

show subpopulations

Gnomad AFR exome

AF:

0.0476

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000811

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00134

AC:

1952

AN:

1452418

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

856

AN XY:

721954

show subpopulations

Gnomad4 AFR exome

AF:

0.0489

Gnomad4 AMR exome

AF:

0.00249

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000415

Gnomad4 OTH exome

AF:

0.00284

GnomAD4 genome

AF:

0.0129

AC:

1969

AN:

152204

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

943

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0454

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.0149

ESP6500AA

AF:

0.0495

AC:

198

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00420

AC:

508

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000278

EpiControl

AF:

0.000181

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0068

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.18

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.10

REVEL

Benign

0.25

Sift

Benign

0.77

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.11

MVP

0.31

MPC

0.12

ClinPred

0.010

GERP RS

5.5

Varity_R

0.073

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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