rs1238975016

Variant names:

• chr1-207321786-C-G
• rs1238975016
• NM_000574.5:c.21C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-207321786-C-G
• chr1-207321786-C-T

Variant summary

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

The NM_000574.5(CD55):​c.21C>G​(p.Ser7Arg) 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. Synonymous variant affecting the same amino acid position (i.e. S7S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CD55 NM_000574.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000296591 (HGNC:):

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=0.059782445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD55	NM_000574.5	c.21C>G	p.Ser7Arg	missense_variant	Exon 1 of 10	ENST00000367064.9	NP_000565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9	c.21C>G	p.Ser7Arg	missense_variant	Exon 1 of 10	1	NM_000574.5	ENSP00000356031.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T;.;T;.;.;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.58	T;T;T;T;T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.060	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.;.;N;N;.;N
PhyloP100		-0.13
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.91	N;N;N;.;N;N;.
REVEL	Benign	0.020
Sift	Benign	0.31	T;T;T;.;T;T;.
Sift4G	Benign	0.21	T;T;T;.;T;T;.
Polyphen		0.016	B;B;B;.;B;.;.
Vest4		0.080
MutPred		0.44		Loss of glycosylation at S7 (P = 0.0242);Loss of glycosylation at S7 (P = 0.0242);Loss of glycosylation at S7 (P = 0.0242);Loss of glycosylation at S7 (P = 0.0242);Loss of glycosylation at S7 (P = 0.0242);Loss of glycosylation at S7 (P = 0.0242);Loss of glycosylation at S7 (P = 0.0242);
MVP		0.076
MPC		0.13
ClinPred		0.12	T
GERP RS		-7.8
PromoterAI		-0.092	Neutral
Varity_R		0.13
gMVP		0.42
Mutation Taster		=89/11	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: rs1238975016; hg19: chr1-207495131;