chr1-159809122-C-T

Variant names:

• chr1-159809122-C-T
• rs779787477
• NM_001004310.3:c.481C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004310.3(FCRL6):​c.481C>T​(p.Pro161Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: FCRL6 NM_001004310.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.255
• Publications: 1 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038375348).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL6	NM_001004310.3	MANE Select	c.481C>T	p.Pro161Ser	missense	Exon 4 of 10	NP_001004310.2	Q6DN72-1
	FCRL6	NM_001426231.1		c.511C>T	p.Pro171Ser	missense	Exon 5 of 11	NP_001413160.1
	FCRL6	NM_001426232.1		c.502C>T	p.Pro168Ser	missense	Exon 5 of 11	NP_001413161.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL6	ENST00000368106.4	TSL:1 MANE Select	c.481C>T	p.Pro161Ser	missense	Exon 4 of 10	ENSP00000357086.3	Q6DN72-1
	FCRL6	ENST00000339348.9	TSL:1	c.481C>T	p.Pro161Ser	missense	Exon 4 of 9	ENSP00000340949.5	Q6DN72-3
	FCRL6	ENST00000392235.7	TSL:1	c.320-280C>T		intron	N/A	ENSP00000376068.3	Q6DN72-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251268 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461798 Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6 AN XY: 727220

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111952

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.24
DEOGEN2	Benign	0.00073	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.17	N
PhyloP100		-0.26
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.013
Sift	Benign	0.74	T
Sift4G	Benign	0.78	T
Polyphen		0.021	B
Vest4		0.13
MutPred		0.21		Gain of phosphorylation at P161 (P = 0.0318)
MVP		0.072
MPC		0.0093
ClinPred		0.027	T
GERP RS		-1.4
Varity_R		0.019
gMVP		0.14
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs779787477; hg19: chr1-159778912;