1-207337170-C-T

Variant names:

• chr1-207337170-C-T
• rs28371667
• ENST00000465534.5:n.946C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000465534.5(CD55):​n.946C>T variant causes a non coding transcript exon 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 ENST00000465534.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465534.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	NM_000574.5	MANE Select	c.980-159C>T		intron	N/A	NP_000565.1
	CD55	NM_001300902.2		c.980-159C>T		intron	N/A	NP_001287831.1
	CD55	NM_001114752.3		c.980-159C>T		intron	N/A	NP_001108224.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	ENST00000465534.5	TSL:1	n.946C>T		non_coding_transcript_exon	Exon 5 of 8
	CD55	ENST00000476590.1	TSL:1	n.946C>T		non_coding_transcript_exon	Exon 5 of 7
	CD55	ENST00000367064.9	TSL:1 MANE Select	c.980-159C>T		intron	N/A	ENSP00000356031.4

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

African (AFR) AF: 0.00387 AC: 49 AN: 12648

American (AMR) AF: 0.00891 AC: 165 AN: 18520

Ashkenazi Jewish (ASJ) AF: 0.0217 AC: 298 AN: 13754

East Asian (EAS) AF: 0.00 AC: 0 AN: 31506

South Asian (SAS) AF: 0.00209 AC: 98 AN: 46912

European-Finnish (FIN) AF: 0.0304 AC: 1080 AN: 35574

Middle Eastern (MID) AF: 0.00690 AC: 25 AN: 3624

European-Non Finnish (NFE) AF: 0.0194 AC: 5405 AN: 279240

Other (OTH) AF: 0.0170 AC: 455 AN: 26760

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

African (AFR) AF: 0.00390 AC: 162 AN: 41572

American (AMR) AF: 0.0107 AC: 163 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4820

European-Finnish (FIN) AF: 0.0239 AC: 254 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0201 AC: 1366 AN: 68004

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.0148 Hom.: 3

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
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
PhyloP100		0.27
Sift4G	Benign	0.47	T
Vest4		0.086
MVP		0.67
GERP RS		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs28371667; hg19: chr1-207510515;