rs28371667

chr1-207337170-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000574.5(CD55):c.980-159C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 620,816 control chromosomes in the GnomAD database, including 98 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 0.014 (26 hom., cov: 32)
  • Exomes 𝑓: 0.016 (72 hom.)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038772523).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0135 (2062/152278) while in subpopulation NFE AF= 0.0201 (1366/68004). AF 95% confidence interval is 0.0192. There are 26 homozygotes in gnomad4. There are 953 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 26 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD55	NM_000574.5	c.980-159C>T		intron_variant		ENST00000367064.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD55	ENST00000367064.9	c.980-159C>T		intron_variant		1	NM_000574.5	P2

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2062 AN: 152160 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0162 AC: 7575 AN: 468538 Hom.: 72 Cov.: 5 AF XY: 0.0154 AC XY: 3838 AN XY: 249108

Gnomad4 AFR exome AF: 0.00387

Gnomad4 AMR exome AF: 0.00891

Gnomad4 ASJ exome AF: 0.0217

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00209

Gnomad4 FIN exome AF: 0.0304

Gnomad4 NFE exome AF: 0.0194

Gnomad4 OTH exome AF: 0.0170

GnomAD4 genome AF: 0.0135 AC: 2062 AN: 152278 Hom.: 26 Cov.: 32 AF XY: 0.0128 AC XY: 953 AN XY: 74460

Gnomad4 AFR AF: 0.00390

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.0239

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0151 Hom.: 2

Bravo AF: 0.0123

TwinsUK AF: 0.0218 AC: 81

ALSPAC AF: 0.0187 AC: 72

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.6
Dann	Benign	0.70
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0039	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
Sift4G	Benign	0.47	T
Vest4		0.086
MVP		0.67
GERP RS		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs28371667; hg19: chr1-207510515;