Genetic Variant NM_031281.3:c.2240-91A>T (chr1-157521383-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031281.3(FCRL5):c.2240-91A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 1,418,094 control chromosomes in the GnomAD database, including 439,064 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 38902 hom., cov: 33)

Exomes 𝑓: 0.79 ( 400162 hom. )

Consequence

FCRL5
NM_031281.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.586

Publications

7 publications found

Variant links:

Genes affected

FCRL5 (HGNC:18508): (Fc receptor like 5) This gene encodes a member of the immunoglobulin receptor superfamily and the Fc-receptor like family. This gene and several other Fc receptor-like gene members are clustered on the long arm of chromosome 1. The encoded protein is a single-pass type I membrane protein and contains 8 immunoglobulin-like C2-type domains. This gene is implicated in B cell development and lymphomagenesis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Sep 2010]

FCRL5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL5	NM_031281.3	MANE Select	c.2240-91A>T		intron	N/A	NP_112571.2	Q96RD9-1
	FCRL5	NM_001195388.2		c.2240-91A>T		intron	N/A	NP_001182317.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCRL5	ENST00000361835.8	TSL:1 MANE Select	c.2240-91A>T	intron	N/A	ENSP00000354691.3	Q96RD9-1
FCRL5	ENST00000908742.1		c.2240-91A>T	intron	N/A	ENSP00000578801.1
FCRL5	ENST00000461387.5	TSL:2	n.1412A>T	non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes

AF:

0.689

AC:

104801

AN:

152058

Hom.:

38904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.757

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.845

Gnomad FIN

AF:

0.857

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.806

Gnomad OTH

AF:

0.721

GnomAD4 exome

AF:

0.792

AC:

1002304

AN:

1265918

Hom.:

400162

Cov.:

AF XY:

0.794

AC XY:

490876

AN XY:

618006

show subpopulations

African (AFR)

AF:

0.361

AC:

10067

AN:

27872

American (AMR)

AF:

0.788

AC:

16588

AN:

21044

Ashkenazi Jewish (ASJ)

AF:

0.837

AC:

15746

AN:

18808

East Asian (EAS)

AF:

0.761

AC:

27186

AN:

35746

South Asian (SAS)

AF:

0.844

AC:

51938

AN:

61556

European-Finnish (FIN)

AF:

0.856

AC:

38864

AN:

45376

Middle Eastern (MID)

AF:

0.789

AC:

4057

AN:

5142

European-Non Finnish (NFE)

AF:

0.799

AC:

797009

AN:

997690

Other (OTH)

AF:

0.775

AC:

40849

AN:

52684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

9762

19524

29287

39049

48811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19180

38360

57540

76720

95900

<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:

0.689

AC:

104817

AN:

152176

Hom.:

38902

Cov.:

AF XY:

0.695

AC XY:

51720

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.382

AC:

15851

AN:

41466

American (AMR)

AF:

0.757

AC:

11584

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.840

AC:

2916

AN:

3470

East Asian (EAS)

AF:

0.775

AC:

4024

AN:

5192

South Asian (SAS)

AF:

0.845

AC:

4083

AN:

4832

European-Finnish (FIN)

AF:

0.857

AC:

9085

AN:

10598

Middle Eastern (MID)

AF:

0.779

AC:

229

AN:

294

European-Non Finnish (NFE)

AF:

0.806

AC:

54813

AN:

68006

Other (OTH)

AF:

0.720

AC:

1520

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1456

2912

4369

5825

7281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.744

Hom.:

5486

Bravo

AF:

0.667

Asia WGS

AF:

0.773

AC:

2688

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.1

(source)

DANN

Benign

0.67

PhyloP100

0.59

Mutation Taster

=100/0

polymorphism (auto)

(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

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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