1-207322082-G-T

Variant names:

• chr1-207322082-G-T
• rs7533852
• NM_000574.5:c.100+217G>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.100+217G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,994 control chromosomes in the GnomAD database, including 12,629 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 0.40 (12629 hom., cov: 32)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.443 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.100+217G>T		intron	N/A	NP_000565.1
	CD55	NM_001300902.2		c.100+217G>T		intron	N/A	NP_001287831.1
	CD55	NM_001114752.3		c.100+217G>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.100+217G>T		intron	N/A	ENSP00000356031.4
	CD55	ENST00000367063.6	TSL:1	c.100+217G>T		intron	N/A	ENSP00000356030.2
	CD55	ENST00000314754.12	TSL:1	c.100+217G>T		intron	N/A	ENSP00000316333.8

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60704 AN: 151876 Hom.: 12615 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.400 AC: 60742 AN: 151994 Hom.: 12629 Cov.: 32 AF XY: 0.400 AC XY: 29684 AN XY: 74294

African (AFR) AF: 0.289 AC: 11988 AN: 41478

American (AMR) AF: 0.452 AC: 6919 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1895 AN: 5152

South Asian (SAS) AF: 0.392 AC: 1890 AN: 4824

European-Finnish (FIN) AF: 0.450 AC: 4749 AN: 10542

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29936 AN: 67918

Other (OTH) AF: 0.451 AC: 951 AN: 2110

Alfa AF: 0.341 Hom.: 3373

Bravo AF: 0.397

Asia WGS AF: 0.339 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		0.30
PromoterAI		-0.049	Neutral
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: rs7533852; hg19: chr1-207495427; COSMIC: COSV58577126; COSMIC: COSV58577126;