8-123975164-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60

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 -14 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_single_submitter, 1 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 GnomAd at 37 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FER1L6	ENST00000522917.5	c.541A>G	p.Asn181Asp	missense_variant	8/41	1	NM_001039112.2	P1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1958 AN: 152086 Hom.: 37 Cov.: 30

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.: 17 AF XY: 0.00244 AC XY: 322 AN XY: 132180

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.: 34 Cov.: 29 AF XY: 0.00119 AC XY: 856 AN XY: 721954

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.: 38 Cov.: 30 AF XY: 0.0127 AC XY: 943 AN XY: 74438

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.: 12

Bravo AF: 0.0149

ESP6500AA AF: 0.0495 AC: 198

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00420 AC: 508

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000278

EpiControl AF: 0.000181

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	19
Dann	Benign	0.95
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.18	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.25
Sift	Benign	0.77	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.31
MPC		0.12
ClinPred		0.010	T
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

Other links and lift over

dbSNP: rs77810887; hg19: chr8-124987404;