NM_000574.5:c.664+111C>T

Variant names:

• chr1-207326948-C-T
• rs4844591
• NM_000574.5:c.664+111C>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.664+111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 648,604 control chromosomes in the GnomAD database, including 155,984 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 0.69 (36903 hom., cov: 32)
  • Exomes 𝑓: 0.69 (119081 hom.)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 19 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 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.664+111C>T		intron	N/A	NP_000565.1
	CD55	NM_001300902.2		c.664+111C>T		intron	N/A	NP_001287831.1
	CD55	NM_001114752.3		c.664+111C>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.664+111C>T		intron	N/A	ENSP00000356031.4
	CD55	ENST00000367063.6	TSL:1	c.664+111C>T		intron	N/A	ENSP00000356030.2
	CD55	ENST00000314754.12	TSL:1	c.664+111C>T		intron	N/A	ENSP00000316333.8

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105173 AN: 151942 Hom.: 36869 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.733

GnomAD4 exome AF: 0.687 AC: 340932 AN: 496544 Hom.: 119081 AF XY: 0.684 AC XY: 181636 AN XY: 265638

African (AFR) AF: 0.671 AC: 8111 AN: 12094

American (AMR) AF: 0.664 AC: 12212 AN: 18378

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 12409 AN: 14430

East Asian (EAS) AF: 0.522 AC: 15359 AN: 29448

South Asian (SAS) AF: 0.585 AC: 24776 AN: 42380

European-Finnish (FIN) AF: 0.748 AC: 29044 AN: 38818

Middle Eastern (MID) AF: 0.810 AC: 2887 AN: 3564

European-Non Finnish (NFE) AF: 0.700 AC: 217980 AN: 311582

Other (OTH) AF: 0.702 AC: 18154 AN: 25850

GnomAD4 genome AF: 0.692 AC: 105266 AN: 152060 Hom.: 36903 Cov.: 32 AF XY: 0.689 AC XY: 51199 AN XY: 74318

African (AFR) AF: 0.684 AC: 28350 AN: 41452

American (AMR) AF: 0.696 AC: 10632 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2984 AN: 3472

East Asian (EAS) AF: 0.425 AC: 2199 AN: 5172

South Asian (SAS) AF: 0.574 AC: 2769 AN: 4826

European-Finnish (FIN) AF: 0.752 AC: 7944 AN: 10568

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47856 AN: 67978

Other (OTH) AF: 0.732 AC: 1547 AN: 2112

Alfa AF: 0.700 Hom.: 142429

Bravo AF: 0.690

Asia WGS AF: 0.477 AC: 1664 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	2.1
DANN	Benign	0.53
PhyloP100		-0.18
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: rs4844591; hg19: chr1-207500293;