1-207337203-A-G

Position:

• chr1-207337203-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367064.9(CD55):​c.980-126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 686,688 control chromosomes in the GnomAD database, including 164,550 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 (36889 hom., cov: 32)
  • Exomes 𝑓: 0.69 (127661 hom.)
• Consequence: CD55 ENST00000367064.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=0.0028584003).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD55	NM_000574.5	c.980-126A>G		intron_variant		ENST00000367064.9	NP_000565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9	c.980-126A>G		intron_variant		1	NM_000574.5	ENSP00000356031	P2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105149 AN: 151924 Hom.: 36855 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.732

GnomAD4 exome AF: 0.686 AC: 367033 AN: 534646 Hom.: 127661 Cov.: 6 AF XY: 0.683 AC XY: 195495 AN XY: 286250

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.675

Gnomad4 ASJ exome AF: 0.861

Gnomad4 EAS exome AF: 0.513

Gnomad4 SAS exome AF: 0.595

Gnomad4 FIN exome AF: 0.748

Gnomad4 NFE exome AF: 0.702

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.692 AC: 105242 AN: 152042 Hom.: 36889 Cov.: 32 AF XY: 0.689 AC XY: 51187 AN XY: 74314

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.731

Alfa AF: 0.699 Hom.: 5121

Bravo AF: 0.690

TwinsUK AF: 0.685 AC: 2540

ALSPAC AF: 0.682 AC: 2627

Asia WGS AF: 0.477 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.76
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0029	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
Sift4G	Benign	0.94	T
Vest4		0.021
MVP		0.59
GERP RS		-1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10746462; hg19: chr1-207510548; COSMIC: COSV58576454; COSMIC: COSV58576454;