1-207353248-G-A

Variant names:

• chr1-207353248-G-A
• rs2135923
• NM_000574.5:c.1082-6298G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000574.5(CD55):​c.1082-6298G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,464 control chromosomes in the GnomAD database, including 6,153 homozygotes. 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: 𝑓 0.27 (6153 hom., cov: 29)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770
• Publications: 13 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	NM_000574.5	MANE Select	c.1082-6298G>A		intron	N/A	NP_000565.1
	CD55	NM_001114752.3		c.1200-6298G>A		intron	N/A	NP_001108224.1
	CD55	NM_001300903.2		c.1196+5687G>A		intron	N/A	NP_001287832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	ENST00000367064.9	TSL:1 MANE Select	c.1082-6298G>A		intron	N/A	ENSP00000356031.4
	CD55	ENST00000314754.12	TSL:1	c.1200-6298G>A		intron	N/A	ENSP00000316333.8
	CD55	ENST00000391921.9	TSL:1	c.890-6298G>A		intron	N/A	ENSP00000375788.4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40669 AN: 151350 Hom.: 6158 Cov.: 29

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.269 AC: 40679 AN: 151464 Hom.: 6153 Cov.: 29 AF XY: 0.273 AC XY: 20193 AN XY: 73962

African (AFR) AF: 0.180 AC: 7440 AN: 41236

American (AMR) AF: 0.290 AC: 4424 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 487 AN: 3466

East Asian (EAS) AF: 0.576 AC: 2962 AN: 5144

South Asian (SAS) AF: 0.422 AC: 2016 AN: 4782

European-Finnish (FIN) AF: 0.247 AC: 2584 AN: 10466

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20035 AN: 67838

Other (OTH) AF: 0.245 AC: 514 AN: 2096

Alfa AF: 0.275 Hom.: 4048

Bravo AF: 0.267

Asia WGS AF: 0.508 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.41
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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: rs2135923; hg19: chr1-207526593;