rs60822373

Variant names:

• chr1-207331122-G-C
• rs60822373
• NM_000574.5:c.679G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-207331122-G-C
• chr1-207331122-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000574.5(CD55):​c.679G>C​(p.Ala227Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,611,430 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (10 hom.)
• Consequence: CD55 NM_000574.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.116
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0067967772).
• BP6: Variant 1-207331122-G-C is Benign according to our data. Variant chr1-207331122-G-C is described in ClinVar as Benign. ClinVar VariationId is 1164353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0055 (837/152158) while in subpopulation AFR AF = 0.0183 (760/41488). AF 95% confidence interval is 0.0172. There are 8 homozygotes in GnomAd4. There are 413 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.679G>C	p.Ala227Pro	missense	Exon 6 of 10	NP_000565.1
	CD55	NM_001300902.2		c.679G>C	p.Ala227Pro	missense	Exon 6 of 10	NP_001287831.1
	CD55	NM_001114752.3		c.679G>C	p.Ala227Pro	missense	Exon 6 of 11	NP_001108224.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	ENST00000367064.9	TSL:1 MANE Select	c.679G>C	p.Ala227Pro	missense	Exon 6 of 10	ENSP00000356031.4
	CD55	ENST00000367063.6	TSL:1	c.679G>C	p.Ala227Pro	missense	Exon 6 of 10	ENSP00000356030.2
	CD55	ENST00000314754.12	TSL:1	c.679G>C	p.Ala227Pro	missense	Exon 6 of 11	ENSP00000316333.8

Frequencies

GnomAD3 genomes AF: 0.00545 AC: 828 AN: 152040 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00164 AC: 411 AN: 250250 AF XY: 0.00112

Gnomad AFR exome AF: 0.0192

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00239

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000984

GnomAD4 exome AF: 0.000624 AC: 911 AN: 1459272 Hom.: 10 Cov.: 30 AF XY: 0.000565 AC XY: 410 AN XY: 725838

African (AFR) AF: 0.0184 AC: 614 AN: 33410

American (AMR) AF: 0.00171 AC: 76 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 45 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.0000467 AC: 4 AN: 85718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00504 AC: 29 AN: 5758

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1110546

Other (OTH) AF: 0.00144 AC: 87 AN: 60300

GnomAD4 genome AF: 0.00550 AC: 837 AN: 152158 Hom.: 8 Cov.: 32 AF XY: 0.00555 AC XY: 413 AN XY: 74394

African (AFR) AF: 0.0183 AC: 760 AN: 41488

American (AMR) AF: 0.00320 AC: 49 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68008

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.000471 Hom.: 1

Bravo AF: 0.00629

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0195 AC: 86

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00204 AC: 248

Asia WGS AF: 0.00260 AC: 10 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.72
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N
PhyloP100		0.12
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.12
Sift	Benign	0.17	T
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.18
MVP		0.66
MPC		0.54
ClinPred		0.020	T
GERP RS		2.0
Varity_R		0.22
gMVP		0.56
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs60822373; hg19: chr1-207504467;