1-207321789-G-A

Variant names:

• chr1-207321789-G-A
• rs1654413389
• NM_000574.5:c.24G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000574.5(CD55):​c.24G>A​(p.Val8Val) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD55 NM_000574.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.482
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-207321789-G-A is Benign according to our data. Variant chr1-207321789-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2979629.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD55	NM_000574.5	c.24G>A	p.Val8Val	synonymous_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.24G>A	p.Val8Val	synonymous_variant	Exon 1 of 10	1	NM_000574.5	ENSP00000356031.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1370358 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 675934

African (AFR) AF: 0.00 AC: 0 AN: 29920

American (AMR) AF: 0.00 AC: 0 AN: 34450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24488

East Asian (EAS) AF: 0.00 AC: 0 AN: 34610

South Asian (SAS) AF: 0.00 AC: 0 AN: 78102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073226

Other (OTH) AF: 0.00 AC: 0 AN: 57150

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 22, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.4
DANN	Benign	0.77
PhyloP100		-0.48
PromoterAI		-0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=99/1	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: rs1654413389; hg19: chr1-207495134;