chr1-207321769-A-G

Position:

• chr1-207321769-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000574.5(CD55):​c.4A>G​(p.Thr2Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T2T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CD55 NM_000574.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.663

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]

LOC107985251 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13509688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD55	NM_000574.5	c.4A>G	p.Thr2Ala	missense_variant	1/10	ENST00000367064.9
LOC107985251	XR_007066838.1	n.361T>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD55	ENST00000367064.9	c.4A>G	p.Thr2Ala	missense_variant	1/10	1	NM_000574.5	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.4A>G (p.T2A) alteration is located in exon 1 (coding exon 1) of the CD55 gene. This alteration results from a A to G substitution at nucleotide position 4, causing the threonine (T) at amino acid position 2 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.4
DANN	Benign	0.90
DEOGEN2	Benign	0.20	T;.;T;.;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.59	T;T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;.;N;N;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.39	N;N;N;.;N;N;.
REVEL	Benign	0.031
Sift	Pathogenic	0.0	D;D;D;.;D;D;.
Sift4G	Uncertain	0.033	D;D;D;.;D;D;.
Polyphen		0.035	B;B;P;.;B;.;.
Vest4		0.052
MutPred		0.32		Loss of glycosylation at T2 (P = 0.0157);Loss of glycosylation at T2 (P = 0.0157);Loss of glycosylation at T2 (P = 0.0157);Loss of glycosylation at T2 (P = 0.0157);Loss of glycosylation at T2 (P = 0.0157);Loss of glycosylation at T2 (P = 0.0157);Loss of glycosylation at T2 (P = 0.0157);
MVP		0.21
MPC		0.44
ClinPred		0.46	T
GERP RS		-2.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.8
Varity_R		0.10
gMVP		0.28

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-207495114;