1-207337251-G-C

Variant names:

• chr1-207337251-G-C
• rs10746463
• NM_000574.5:c.980-78G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001300902.2(CD55):​c.980-78G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 781,298 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: CD55 NM_001300902.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093872875).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300902.2. 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.980-78G>C		intron	N/A	NP_000565.1
	CD55	NM_001300902.2		c.980-78G>C		intron	N/A	NP_001287831.1
	CD55	NM_001114752.3		c.980-78G>C		intron	N/A	NP_001108224.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	ENST00000367064.9	TSL:1 MANE Select	c.980-78G>C		intron	N/A	ENSP00000356031.4
	CD55	ENST00000367063.6	TSL:1	c.980-78G>C		intron	N/A	ENSP00000356030.2
	CD55	ENST00000314754.12	TSL:1	c.980-78G>C		intron	N/A	ENSP00000316333.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000128 AC: 1 AN: 781298 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 412808

African (AFR) AF: 0.00 AC: 0 AN: 19868

American (AMR) AF: 0.00 AC: 0 AN: 38820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19830

East Asian (EAS) AF: 0.00 AC: 0 AN: 36432

South Asian (SAS) AF: 0.00 AC: 0 AN: 69246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4344

European-Non Finnish (NFE) AF: 0.00000198 AC: 1 AN: 503780

Other (OTH) AF: 0.00 AC: 0 AN: 37660

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.041
DANN	Benign	0.44
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.094	T
PhyloP100		-2.5
Sift4G	Benign	0.28	T
Vest4		0.084
MVP		0.69
GERP RS		-6.8
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: rs10746463; hg19: chr1-207510596;