1-207337203-A-T

Variant names:

• chr1-207337203-A-T
• rs10746462
• ENST00000465534.5:n.979A>T

Variant summary

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

The ENST00000465534.5(CD55):​n.979A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD55 ENST00000465534.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 15 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=0.09325799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD55	NM_000574.5	c.980-126A>T		intron_variant	Intron 7 of 9	ENST00000367064.9	NP_000565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9	c.980-126A>T		intron_variant	Intron 7 of 9	1	NM_000574.5	ENSP00000356031.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 535248 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 286568

African (AFR) AF: 0.00 AC: 0 AN: 14572

American (AMR) AF: 0.00 AC: 0 AN: 26152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15198

East Asian (EAS) AF: 0.00 AC: 0 AN: 33496

South Asian (SAS) AF: 0.00 AC: 0 AN: 53330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3770

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 316860

Other (OTH) AF: 0.00 AC: 0 AN: 29358

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.86
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.093	T
PhyloP100		-1.1
Sift4G	Benign	0.21	T
Vest4		0.14
MVP		0.54
GERP RS		-1.5
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: rs10746462; hg19: chr1-207510548;