4-70234031-C-G

Variant names:

• chr4-70234031-C-G
• rs766366241
• NM_152997.4:c.102C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152997.4(FDCSP):​c.102C>G​(p.Ser34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,603,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FDCSP NM_152997.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 2 publications found

Genes affected

FDCSP (HGNC:19215): (follicular dendritic cell secreted protein) This gene encodes a small secreted protein that is expressed in follicular dendritic cells. This protein specifically binds to activated B cells, and functions as a regulator of antibody responses. It is also thought to contribute to tumor metastases by promoting cancer cell migration and invasion. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16150266).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152997.4. 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
	FDCSP	NM_152997.4	MANE Select	c.102C>G	p.Ser34Arg	missense	Exon 4 of 5	NP_694542.1	Q8NFU4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDCSP	ENST00000317987.6	TSL:1 MANE Select	c.102C>G	p.Ser34Arg	missense	Exon 4 of 5	ENSP00000318437.5	Q8NFU4

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151534 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000818 AC: 2 AN: 244374 AF XY: 0.00000757

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452284 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722206

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32968

American (AMR) AF: 0.00 AC: 0 AN: 43690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25740

East Asian (EAS) AF: 0.00 AC: 0 AN: 39468

South Asian (SAS) AF: 0.00 AC: 0 AN: 84172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107326

Other (OTH) AF: 0.00 AC: 0 AN: 59974

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151534 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73952

African (AFR) AF: 0.00 AC: 0 AN: 41326

American (AMR) AF: 0.00 AC: 0 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67710

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.0000226 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.82	T
PhyloP100		-0.87
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.076
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.15		Gain of glycosylation at S30 (P = 0.0046)
MVP		0.10
MPC		0.12
ClinPred		0.93	D
GERP RS		-2.1
Varity_R		0.72
gMVP		0.14
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs766366241; hg19: chr4-71099748;