1-207321879-C-T

Variant names:

• chr1-207321879-C-T
• rs28371587
• NM_000574.5:c.100+14C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000574.5(CD55):​c.100+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00068 in 1,507,498 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00043 (3 hom.)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30
• Publications: 2 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

LOC107985251 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-207321879-C-T is Benign according to our data. Variant chr1-207321879-C-T is described in ClinVar as [Benign]. Clinvar id is 1169262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00294 (447/152234) while in subpopulation AFR AF = 0.00893 (371/41554). AF 95% confidence interval is 0.00818. There are 1 homozygotes in GnomAd4. There are 221 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD55	NM_000574.5	c.100+14C>T		intron_variant	Intron 1 of 9	ENST00000367064.9	NP_000565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9	c.100+14C>T		intron_variant	Intron 1 of 9	1	NM_000574.5	ENSP00000356031.4

Frequencies

GnomAD3 genomes AF: 0.00294 AC: 447 AN: 152118 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.000616 AC: 69 AN: 111958 AF XY: 0.000450

Gnomad AFR exome AF: 0.00803

Gnomad AMR exome AF: 0.000874

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000192

Gnomad OTH exome AF: 0.000284

GnomAD4 exome AF: 0.000426 AC: 578 AN: 1355264 Hom.: 3 Cov.: 28 AF XY: 0.000376 AC XY: 251 AN XY: 667500

African (AFR) AF: 0.00898 AC: 269 AN: 29962

American (AMR) AF: 0.00115 AC: 37 AN: 32202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23704

East Asian (EAS) AF: 0.00 AC: 0 AN: 34698

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34380

Middle Eastern (MID) AF: 0.00252 AC: 10 AN: 3964

European-Non Finnish (NFE) AF: 0.000183 AC: 194 AN: 1062984

Other (OTH) AF: 0.00119 AC: 67 AN: 56390

GnomAD4 genome AF: 0.00294 AC: 447 AN: 152234 Hom.: 1 Cov.: 33 AF XY: 0.00297 AC XY: 221 AN XY: 74446

African (AFR) AF: 0.00893 AC: 371 AN: 41554

American (AMR) AF: 0.00314 AC: 48 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68000

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.000172 Hom.: 0

Bravo AF: 0.00325

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.0
DANN	Benign	0.95
PhyloP100		-1.3
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		3.3
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: rs28371587; hg19: chr1-207495224;