rs28371626

Variant names:

• chr1-207337515-G-A
• rs28371626
• NM_000574.5:c.1060+106G>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.1060+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 678,418 control chromosomes in the GnomAD database, including 378 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 0.023 (81 hom., cov: 32)
  • Exomes 𝑓: 0.028 (297 hom.)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 1 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0568 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	NM_000574.5	MANE Select	c.1060+106G>A		intron	N/A	NP_000565.1	P08174-1
	CD55	NM_001300902.2		c.1060+106G>A		intron	N/A	NP_001287831.1	B1AP13
	CD55	NM_001114752.3		c.1060+106G>A		intron	N/A	NP_001108224.1	P08174-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	ENST00000367064.9	TSL:1 MANE Select	c.1060+106G>A		intron	N/A	ENSP00000356031.4	P08174-1
	CD55	ENST00000367063.6	TSL:1	c.1060+106G>A		intron	N/A	ENSP00000356030.2	B1AP13
	CD55	ENST00000314754.12	TSL:1	c.1060+106G>A		intron	N/A	ENSP00000316333.8	P08174-2

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3503 AN: 152064 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.00377

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0186

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.0277 AC: 14553 AN: 526236 Hom.: 297 Cov.: 6 AF XY: 0.0276 AC XY: 7830 AN XY: 283764

African (AFR) AF: 0.00475 AC: 64 AN: 13476

American (AMR) AF: 0.0165 AC: 415 AN: 25146

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 850 AN: 15692

East Asian (EAS) AF: 0.0000935 AC: 3 AN: 32096

South Asian (SAS) AF: 0.0122 AC: 648 AN: 52980

European-Finnish (FIN) AF: 0.0628 AC: 2738 AN: 43596

Middle Eastern (MID) AF: 0.0634 AC: 239 AN: 3770

European-Non Finnish (NFE) AF: 0.0283 AC: 8799 AN: 310658

Other (OTH) AF: 0.0277 AC: 797 AN: 28822

GnomAD4 genome AF: 0.0230 AC: 3501 AN: 152182 Hom.: 81 Cov.: 32 AF XY: 0.0241 AC XY: 1791 AN XY: 74398

African (AFR) AF: 0.00376 AC: 156 AN: 41530

American (AMR) AF: 0.0186 AC: 284 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0127 AC: 61 AN: 4820

European-Finnish (FIN) AF: 0.0652 AC: 689 AN: 10568

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0283 AC: 1924 AN: 68014

Other (OTH) AF: 0.0275 AC: 58 AN: 2112

Alfa AF: 0.0238 Hom.: 35

Bravo AF: 0.0186

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.3
DANN	Benign	0.81
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs28371626; hg19: chr1-207510860;