NM_000574.5:c.854-239C>T

Variant names:

• chr1-207336454-C-T
• rs1507761
• NM_000574.5:c.854-239C>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.854-239C>T 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 151,972 control chromosomes in the GnomAD database, including 6,191 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 (6191 hom., cov: 31)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 12 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD55	NM_000574.5	c.854-239C>T		intron_variant	Intron 6 of 9	ENST00000367064.9	NP_000565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9	c.854-239C>T		intron_variant	Intron 6 of 9	1	NM_000574.5	ENSP00000356031.4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40903 AN: 151854 Hom.: 6195 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.269 AC: 40918 AN: 151972 Hom.: 6191 Cov.: 31 AF XY: 0.274 AC XY: 20334 AN XY: 74262

African (AFR) AF: 0.182 AC: 7542 AN: 41452

American (AMR) AF: 0.291 AC: 4437 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3468

East Asian (EAS) AF: 0.575 AC: 2968 AN: 5164

South Asian (SAS) AF: 0.423 AC: 2040 AN: 4824

European-Finnish (FIN) AF: 0.249 AC: 2622 AN: 10548

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

European-Non Finnish (NFE) AF: 0.296 AC: 20083 AN: 67932

Other (OTH) AF: 0.246 AC: 521 AN: 2114

Alfa AF: 0.270 Hom.: 8747

Bravo AF: 0.267

Asia WGS AF: 0.508 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.68
PhyloP100		-0.24
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: rs1507761; hg19: chr1-207509799;