NM_031281.3:c.805G>A

Variant names:

• chr1-157544301-C-T
• rs12036228
• NM_031281.3:c.805G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031281.3(FCRL5):​c.805G>A​(p.Val269Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,613,592 control chromosomes in the GnomAD database, including 36,126 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4061 hom., cov: 32)
  • Exomes 𝑓: 0.21 (32065 hom.)
• Consequence: FCRL5 NM_031281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 30 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034855008).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL5	NM_031281.3	MANE Select	c.805G>A	p.Val269Ile	missense	Exon 5 of 17	NP_112571.2
	FCRL5	NM_001195388.2		c.805G>A	p.Val269Ile	missense	Exon 5 of 17	NP_001182317.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL5	ENST00000361835.8	TSL:1 MANE Select	c.805G>A	p.Val269Ile	missense	Exon 5 of 17	ENSP00000354691.3
	FCRL5	ENST00000368190.7	TSL:1	c.805G>A	p.Val269Ile	missense	Exon 5 of 10	ENSP00000357173.3
	FCRL5	ENST00000368189.3	TSL:1	c.805G>A	p.Val269Ile	missense	Exon 5 of 8	ENSP00000357172.3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34349 AN: 152032 Hom.: 4064 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0830

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.252

GnomAD2 exomes AF: 0.189 AC: 47581 AN: 251146 AF XY: 0.191

Gnomad AFR exome AF: 0.297

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.0849

Gnomad FIN exome AF: 0.195

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.206 AC: 300463 AN: 1461442 Hom.: 32065 Cov.: 33 AF XY: 0.205 AC XY: 148855 AN XY: 727034

African (AFR) AF: 0.297 AC: 9935 AN: 33466

American (AMR) AF: 0.134 AC: 5975 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 5887 AN: 26132

East Asian (EAS) AF: 0.0781 AC: 3102 AN: 39700

South Asian (SAS) AF: 0.177 AC: 15249 AN: 86246

European-Finnish (FIN) AF: 0.197 AC: 10532 AN: 53420

Middle Eastern (MID) AF: 0.288 AC: 1659 AN: 5766

European-Non Finnish (NFE) AF: 0.212 AC: 235277 AN: 1111608

Other (OTH) AF: 0.213 AC: 12847 AN: 60380

GnomAD4 genome AF: 0.226 AC: 34359 AN: 152150 Hom.: 4061 Cov.: 32 AF XY: 0.221 AC XY: 16414 AN XY: 74366

African (AFR) AF: 0.294 AC: 12192 AN: 41488

American (AMR) AF: 0.184 AC: 2805 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3470

East Asian (EAS) AF: 0.0828 AC: 428 AN: 5170

South Asian (SAS) AF: 0.160 AC: 773 AN: 4828

European-Finnish (FIN) AF: 0.209 AC: 2209 AN: 10580

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14267 AN: 68018

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.206 Hom.: 3061

Bravo AF: 0.227

TwinsUK AF: 0.226 AC: 837

ALSPAC AF: 0.221 AC: 852

ESP6500AA AF: 0.294 AC: 1295

ESP6500EA AF: 0.214 AC: 1842

ExAC AF: 0.192 AC: 23339

Asia WGS AF: 0.156 AC: 545 AN: 3478

EpiCase AF: 0.218

EpiControl AF: 0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.028
DANN	Benign	0.75
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.68	N
PhyloP100		-2.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.023
Sift	Benign	0.69	T
Sift4G	Benign	0.47	T
Polyphen		0.045	B
Vest4		0.023
MPC		0.061
ClinPred		0.0015	T
GERP RS		-1.6
Varity_R		0.011
gMVP		0.089
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12036228; hg19: chr1-157514091; COSMIC: COSV62520687;