8-123970054-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001039112.2(FER1L6):c.404T>C(p.Ile135Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,614,104 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (3 hom.)
• Consequence: FER1L6 NM_001039112.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.208

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0067364573).
• BP6: Variant 8-123970054-T-C is Benign according to our data. Variant chr8-123970054-T-C is described in ClinVar as [Benign]. Clinvar id is 735141.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FER1L6	NM_001039112.2	c.404T>C	p.Ile135Thr	missense_variant	6/41	ENST00000522917.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FER1L6	ENST00000522917.5	c.404T>C	p.Ile135Thr	missense_variant	6/41	1	NM_001039112.2	P1

Frequencies

GnomAD3 genomes AF: 0.00374 AC: 569 AN: 152182 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00100 AC: 250 AN: 249414 Hom.: 1 AF XY: 0.000754 AC XY: 102 AN XY: 135314

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000460 AC: 673 AN: 1461804 Hom.: 3 Cov.: 31 AF XY: 0.000395 AC XY: 287 AN XY: 727220

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000719

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.00378 AC: 575 AN: 152300 Hom.: 4 Cov.: 32 AF XY: 0.00385 AC XY: 287 AN XY: 74486

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00123 Hom.: 1

Bravo AF: 0.00441

ESP6500AA AF: 0.0134 AC: 50

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00122 AC: 147

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000178

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	0.057
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	13
Dann	Benign	0.66
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0067	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.76	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.072
Sift	Benign	0.46	T
Sift4G	Benign	0.39	T
Polyphen		0.023	B
Vest4		0.29
MVP		0.11
MPC		0.15
ClinPred		0.0022	T
GERP RS		2.5
Varity_R		0.038
gMVP		0.26

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

Other links and lift over

dbSNP: rs114920664; hg19: chr8-124982294; COSMIC: COSV101205419;