rs17645

Variant names:

• chr1-26320239-A-G
• rs17645
• NM_001803.3:c.123A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001803.3(CD52):​c.123A>G​(p.Ile41Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,612,100 control chromosomes in the GnomAD database, including 428,050 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.70 (37062 hom., cov: 31)
  • Exomes 𝑓: 0.73 (390988 hom.)
• Consequence: CD52 NM_001803.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0940
• Publications: 36 publications found

Genes affected

CD52 (HGNC:1804): (CD52 molecule) Involved in positive regulation of cytosolic calcium ion concentration. Predicted to be located in extracellular region and plasma membrane. Predicted to be intrinsic component of plasma membrane. Predicted to be active in sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.0592913E-6).
• BP6: Variant 1-26320239-A-G is Benign according to our data. Variant chr1-26320239-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059585.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001803.3. 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
	CD52	NM_001803.3	MANE Select	c.123A>G	p.Ile41Met	missense	Exon 2 of 2	NP_001794.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD52	ENST00000374213.3	TSL:1 MANE Select	c.123A>G	p.Ile41Met	missense	Exon 2 of 2	ENSP00000363330.2
	CD52	ENST00000470468.1	TSL:3	n.296A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105278 AN: 151436 Hom.: 37033 Cov.: 31

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.663

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.698

GnomAD2 exomes AF: 0.669 AC: 167193 AN: 249970 AF XY: 0.671

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.574

Gnomad ASJ exome AF: 0.766

Gnomad EAS exome AF: 0.424

Gnomad FIN exome AF: 0.704

Gnomad NFE exome AF: 0.756

Gnomad OTH exome AF: 0.705

GnomAD4 exome AF: 0.727 AC: 1061486 AN: 1460546 Hom.: 390988 Cov.: 53 AF XY: 0.723 AC XY: 524997 AN XY: 726590

African (AFR) AF: 0.659 AC: 21986 AN: 33356

American (AMR) AF: 0.582 AC: 25824 AN: 44362

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 20063 AN: 26096

East Asian (EAS) AF: 0.423 AC: 16753 AN: 39648

South Asian (SAS) AF: 0.545 AC: 46902 AN: 86010

European-Finnish (FIN) AF: 0.709 AC: 37839 AN: 53392

Middle Eastern (MID) AF: 0.703 AC: 4052 AN: 5760

European-Non Finnish (NFE) AF: 0.761 AC: 845832 AN: 1111578

Other (OTH) AF: 0.700 AC: 42235 AN: 60344

GnomAD4 genome AF: 0.695 AC: 105356 AN: 151554 Hom.: 37062 Cov.: 31 AF XY: 0.687 AC XY: 50871 AN XY: 74062

African (AFR) AF: 0.660 AC: 27255 AN: 41298

American (AMR) AF: 0.648 AC: 9874 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2663 AN: 3462

East Asian (EAS) AF: 0.424 AC: 2177 AN: 5140

South Asian (SAS) AF: 0.525 AC: 2525 AN: 4808

European-Finnish (FIN) AF: 0.697 AC: 7321 AN: 10504

Middle Eastern (MID) AF: 0.669 AC: 194 AN: 290

European-Non Finnish (NFE) AF: 0.754 AC: 51161 AN: 67808

Other (OTH) AF: 0.691 AC: 1452 AN: 2100

Alfa AF: 0.730 Hom.: 116500

Bravo AF: 0.693

TwinsUK AF: 0.766 AC: 2842

ALSPAC AF: 0.758 AC: 2920

ESP6500AA AF: 0.667 AC: 2938

ESP6500EA AF: 0.765 AC: 6583

ExAC AF: 0.671 AC: 81469

Asia WGS AF: 0.459 AC: 1598 AN: 3476

EpiCase AF: 0.758

EpiControl AF: 0.759

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CD52-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.1
DANN	Benign	0.32
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000041	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.094
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.073
Sift	Benign	0.29	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.085
MPC		0.23
ClinPred		0.0027	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.069
gMVP		0.056
Mutation Taster		=95/5	polymorphism (auto)

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: rs17645; hg19: chr1-26646730; COSMIC: COSV57485055; COSMIC: COSV57485055;