8-123975927-T-C

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.713T>C(p.Leu238Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00134 in 1,612,762 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L238L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0072 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (9 hom.)
• Consequence: FER1L6 NM_001039112.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.15

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=0.006888032).
• BP6: Variant 8-123975927-T-C is Benign according to our data. Variant chr8-123975927-T-C is described in ClinVar as [Benign]. Clinvar id is 709350.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00718 (1093/152312) while in subpopulation AFR AF= 0.0251 (1042/41562). AF 95% confidence interval is 0.0238. There are 10 homozygotes in gnomad4. There are 535 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FER1L6	NM_001039112.2	c.713T>C	p.Leu238Pro	missense_variant	9/41	ENST00000522917.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FER1L6	ENST00000522917.5	c.713T>C	p.Leu238Pro	missense_variant	9/41	1	NM_001039112.2	P1

Frequencies

GnomAD3 genomes AF: 0.00714 AC: 1086 AN: 152194 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00180 AC: 446 AN: 248318 Hom.: 2 AF XY: 0.00133 AC XY: 179 AN XY: 134652

Gnomad AFR exome AF: 0.0259

Gnomad AMR exome AF: 0.00120

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: 0.0000355

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.000731 AC: 1067 AN: 1460450 Hom.: 9 Cov.: 31 AF XY: 0.000647 AC XY: 470 AN XY: 726388

Gnomad4 AFR exome AF: 0.0263

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000810

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.00718 AC: 1093 AN: 152312 Hom.: 10 Cov.: 32 AF XY: 0.00718 AC XY: 535 AN XY: 74492

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00237 Hom.: 5

Bravo AF: 0.00829

ExAC AF: 0.00233 AC: 281

Asia WGS AF: 0.00375 AC: 13 AN: 3478

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	0.062
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	20
Dann	Benign	0.83
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.51	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.88	N
REVEL	Benign	0.26
Sift	Benign	0.38	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.42
MVP		0.20
MPC		0.18
ClinPred		0.0056	T
GERP RS		5.3
Varity_R		0.11
gMVP		0.54

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: rs75339130; hg19: chr8-124988167;