Genetic Variant FCRL6:p.Leu108Gln (chr1-159808964-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004310.3(FCRL6):c.323T>A(p.Leu108Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,603,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

FCRL6
NM_001004310.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Publications

0 publications found

Variant links:

Genes affected

FCRL6 (HGNC:31910): (Fc receptor like 6) Enables MHC class II protein binding activity and protein phosphatase binding activity. Predicted to be involved in cell surface receptor signaling pathway. Located in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FCRL6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20227799).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004310.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRL6	NM_001004310.3	MANE Select	c.323T>A	p.Leu108Gln	missense	Exon 4 of 10	NP_001004310.2	Q6DN72-1
FCRL6	NM_001426231.1		c.353T>A	p.Leu118Gln	missense	Exon 5 of 11	NP_001413160.1
FCRL6	NM_001426232.1		c.344T>A	p.Leu115Gln	missense	Exon 5 of 11	NP_001413161.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRL6	ENST00000368106.4	TSL:1 MANE Select	c.323T>A	p.Leu108Gln	missense	Exon 4 of 10	ENSP00000357086.3	Q6DN72-1
FCRL6	ENST00000339348.9	TSL:1	c.323T>A	p.Leu108Gln	missense	Exon 4 of 9	ENSP00000340949.5	Q6DN72-3
FCRL6	ENST00000392235.7	TSL:1	c.320-438T>A		intron	N/A	ENSP00000376068.3	Q6DN72-4

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000177

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000194

AC:

AN:

241682

AF XY:

0.000169

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.000179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000951

Gnomad NFE exome

AF:

0.000332

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000210

AC:

304

AN:

1450970

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

156

AN XY:

721096

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33230

American (AMR)

AF:

0.000206

AC:

AN:

43704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25198

East Asian (EAS)

AF:

0.00

AC:

AN:

39520

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84852

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

52966

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.000244

AC:

270

AN:

1105930

Other (OTH)

AF:

0.000301

AC:

AN:

59868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67968

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000170

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000305

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

Eigen

Benign

0.19

Eigen_PC

Benign

0.025

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.68

M_CAP

Benign

0.021

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

PhyloP100

1.3

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.54

MVP

0.33

MPC

0.044

ClinPred

0.30

GERP RS

4.2

Varity_R

0.52

gMVP

0.18

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over