chr1-157524453-T-C

Position:

• chr1-157524453-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_031281.3(FCRL5):​c.2065A>G​(p.Ile689Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,152 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (11 hom., cov: 33)
  • Exomes 𝑓: 0.00070 (12 hom.)
• Consequence: FCRL5 NM_031281.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.31

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006784886).
• BP6: Variant 1-157524453-T-C is Benign according to our data. Variant chr1-157524453-T-C is described in ClinVar as [Benign]. Clinvar id is 709690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00646 (984/152262) while in subpopulation AFR AF= 0.0228 (947/41556). AF 95% confidence interval is 0.0216. There are 11 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL5	NM_031281.3	c.2065A>G	p.Ile689Val	missense_variant	10/17	ENST00000361835.8	NP_112571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL5	ENST00000361835.8	c.2065A>G	p.Ile689Val	missense_variant	10/17	1	NM_031281.3	ENSP00000354691	P1
FCRL5	ENST00000368190.7	c.2065A>G	p.Ile689Val	missense_variant	10/10	1		ENSP00000357173
FCRL5	ENST00000497286.5	n.1158A>G		non_coding_transcript_exon_variant	2/9	2

Frequencies

GnomAD3 genomes AF: 0.00647 AC: 985 AN: 152144 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00165 AC: 414 AN: 251426 Hom.: 7 AF XY: 0.00108 AC XY: 147 AN XY: 135882

Gnomad AFR exome AF: 0.0234

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000698 AC: 1021 AN: 1461890 Hom.: 12 Cov.: 31 AF XY: 0.000571 AC XY: 415 AN XY: 727248

Gnomad4 AFR exome AF: 0.0261

Gnomad4 AMR exome AF: 0.000872

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.00646 AC: 984 AN: 152262 Hom.: 11 Cov.: 33 AF XY: 0.00638 AC XY: 475 AN XY: 74450

Gnomad4 AFR AF: 0.0228

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00137 Hom.: 1

Bravo AF: 0.00728

ESP6500AA AF: 0.0207 AC: 91

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00210 AC: 255

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0016	T;.
Eigen	Benign	0.063
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.78	T;T
MetaRNN	Benign	0.0068	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.19
Sift	Benign	0.17	T;D
Sift4G	Uncertain	0.011	D;T
Polyphen		1.0	D;B
Vest4		0.47
MVP		0.085
MPC		0.38
ClinPred		0.041	T
GERP RS		4.7
Varity_R		0.053
gMVP		0.066

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs113003110; hg19: chr1-157494243;