chr1-207337350-C-T

Variant names:

• chr1-207337350-C-T
• rs12135160
• NM_000574.5:c.1001C>T

Variant summary

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

The NM_000574.5(CD55):​c.1001C>T​(p.Ser334Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S334P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD55 NM_000574.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 2 publications found

Genes affected

CD55 (HGNC:2665): (CD55 molecule (Cromer blood group)) This gene encodes a glycoprotein involved in the regulation of the complement cascade. Binding of the encoded protein to complement proteins accelerates their decay, thereby disrupting the cascade and preventing damage to host cells. Antigens present on this protein constitute the Cromer blood group system (CROM). Alternative splicing results in multiple transcript variants. The predominant transcript variant encodes a membrane-bound protein, but alternatively spliced transcripts may produce soluble proteins. [provided by RefSeq, Jul 2014]

CD55 Gene-Disease associations (from GenCC):

• protein-losing enteropathy

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

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=0.15342739).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000574.5. 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
	CD55	NM_000574.5	MANE Select	c.1001C>T	p.Ser334Phe	missense	Exon 8 of 10	NP_000565.1	P08174-1
	CD55	NM_001300902.2		c.1001C>T	p.Ser334Phe	missense	Exon 8 of 10	NP_001287831.1	B1AP13
	CD55	NM_001114752.3		c.1001C>T	p.Ser334Phe	missense	Exon 8 of 11	NP_001108224.1	P08174-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	ENST00000367064.9	TSL:1 MANE Select	c.1001C>T	p.Ser334Phe	missense	Exon 8 of 10	ENSP00000356031.4	P08174-1
	CD55	ENST00000367063.6	TSL:1	c.1001C>T	p.Ser334Phe	missense	Exon 8 of 10	ENSP00000356030.2	B1AP13
	CD55	ENST00000314754.12	TSL:1	c.1001C>T	p.Ser334Phe	missense	Exon 8 of 11	ENSP00000316333.8	P08174-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.43
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.027
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.047	D
Polyphen		0.13	B
Vest4		0.16
MutPred		0.34		Loss of glycosylation at S334 (P = 0.0105)
MVP		0.25
MPC		0.55
ClinPred		0.65	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.095
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs12135160; hg19: chr1-207510695; COSMIC: COSV58576732; COSMIC: COSV58576732;