chr1-207321879-C-G

Variant names:

• chr1-207321879-C-G
• rs28371587
• NM_000574.5:c.100+14C>G

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.100+14C>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• 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: Labcorp Genetics (formerly Invitae), Orphanet

LOC107985251 (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 (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD55	NM_000574.5	c.100+14C>G		intron_variant	Intron 1 of 9	ENST00000367064.9	NP_000565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9	c.100+14C>G		intron_variant	Intron 1 of 9	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: 1355266 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 667502

African (AFR) AF: 0.00 AC: 0 AN: 29964

American (AMR) AF: 0.00 AC: 0 AN: 32202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23704

East Asian (EAS) AF: 0.00 AC: 0 AN: 34698

South Asian (SAS) AF: 0.00 AC: 0 AN: 76980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3964

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1062984

Other (OTH) AF: 0.00 AC: 0 AN: 56390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.5
DANN	Benign	0.75
PhyloP100		-1.3
PromoterAI		-0.046	Neutral

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: rs28371587; hg19: chr1-207495224;