chr1-207322784-C-T

Variant names:

• chr1-207322784-C-T
• rs4844590
• NM_000574.5:c.286+217C>T

Variant summary

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

The NM_000574.5(CD55):​c.286+217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,078 control chromosomes in the GnomAD database, including 3,681 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 0.22 (3681 hom., cov: 32)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 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.286+217C>T		intron	N/A	NP_000565.1
	CD55	NM_001300902.2		c.286+217C>T		intron	N/A	NP_001287831.1
	CD55	NM_001114752.3		c.286+217C>T		intron	N/A	NP_001108224.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	ENST00000367064.9	TSL:1 MANE Select	c.286+217C>T		intron	N/A	ENSP00000356031.4
	CD55	ENST00000367063.6	TSL:1	c.286+217C>T		intron	N/A	ENSP00000356030.2
	CD55	ENST00000314754.12	TSL:1	c.286+217C>T		intron	N/A	ENSP00000316333.8

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32709 AN: 151960 Hom.: 3683 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0551

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.215 AC: 32723 AN: 152078 Hom.: 3681 Cov.: 32 AF XY: 0.214 AC XY: 15939 AN XY: 74348

African (AFR) AF: 0.178 AC: 7369 AN: 41450

American (AMR) AF: 0.203 AC: 3101 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1167 AN: 3470

East Asian (EAS) AF: 0.0554 AC: 287 AN: 5182

South Asian (SAS) AF: 0.177 AC: 856 AN: 4826

European-Finnish (FIN) AF: 0.265 AC: 2799 AN: 10570

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16374 AN: 67980

Other (OTH) AF: 0.209 AC: 442 AN: 2110

Alfa AF: 0.215 Hom.: 1561

Bravo AF: 0.207

Asia WGS AF: 0.123 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.8
DANN	Benign	0.70
PhyloP100		0.11
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: rs4844590; hg19: chr1-207496129;