1-207329027-T-G

Variant names:

• chr1-207329027-T-G
• rs6703002
• NM_000574.5:c.665-2081T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000574.5(CD55):​c.665-2081T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,118 control chromosomes in the GnomAD database, including 36,895 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 (36895 hom., cov: 32)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 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.665-2081T>G		intron	N/A	NP_000565.1	P08174-1
	CD55	NM_001300902.2		c.665-2081T>G		intron	N/A	NP_001287831.1	B1AP13
	CD55	NM_001114752.3		c.665-2081T>G		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.665-2081T>G		intron	N/A	ENSP00000356031.4	P08174-1
	CD55	ENST00000367063.6	TSL:1	c.665-2081T>G		intron	N/A	ENSP00000356030.2	B1AP13
	CD55	ENST00000314754.12	TSL:1	c.665-2081T>G		intron	N/A	ENSP00000316333.8	P08174-2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105169 AN: 152000 Hom.: 36861 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.692 AC: 105262 AN: 152118 Hom.: 36895 Cov.: 32 AF XY: 0.689 AC XY: 51207 AN XY: 74364

African (AFR) AF: 0.683 AC: 28361 AN: 41502

American (AMR) AF: 0.696 AC: 10638 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2979 AN: 3466

East Asian (EAS) AF: 0.424 AC: 2188 AN: 5158

South Asian (SAS) AF: 0.573 AC: 2769 AN: 4830

European-Finnish (FIN) AF: 0.751 AC: 7947 AN: 10576

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

European-Non Finnish (NFE) AF: 0.704 AC: 47850 AN: 67990

Other (OTH) AF: 0.732 AC: 1543 AN: 2108

Alfa AF: 0.692 Hom.: 53313

Bravo AF: 0.689

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	-0.81
CADD	Benign	9.0
DANN	Benign	0.53
PhyloP100		-0.078
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6703002;

hg19: chr1-207502372;