rs1071849

Variant names:

• chr1-26320235-A-G
• rs1071849
• NM_001803.3:c.119A>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.119A>G​(p.Asn40Ser) 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 1,612,364 control chromosomes in the GnomAD database, including 428,107 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 (37065 hom., cov: 31)
  • Exomes 𝑓: 0.73 (391042 hom.)
• Consequence: CD52 NM_001803.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.160
• Publications: 42 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=4.305119E-7).
• BP6: Variant 1-26320235-A-G is Benign according to our data. Variant chr1-26320235-A-G is described in ClinVar as [Benign]. Clinvar id is 3059084.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD52	NM_001803.3	c.119A>G	p.Asn40Ser	missense_variant	Exon 2 of 2	ENST00000374213.3	NP_001794.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD52	ENST00000374213.3	c.119A>G	p.Asn40Ser	missense_variant	Exon 2 of 2	1	NM_001803.3	ENSP00000363330.2
CD52	ENST00000470468.1	n.292A>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105287 AN: 151464 Hom.: 37036 Cov.: 31

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.770

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: 0.700

GnomAD2 exomes AF: 0.669 AC: 167316 AN: 250142 AF XY: 0.671

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.574

Gnomad ASJ exome AF: 0.765

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: 1061658 AN: 1460782 Hom.: 391042 Cov.: 54 AF XY: 0.723 AC XY: 525084 AN XY: 726712

African (AFR) AF: 0.659 AC: 22019 AN: 33396

American (AMR) AF: 0.582 AC: 25866 AN: 44420

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 20073 AN: 26110

East Asian (EAS) AF: 0.423 AC: 16759 AN: 39662

South Asian (SAS) AF: 0.545 AC: 46934 AN: 86056

European-Finnish (FIN) AF: 0.709 AC: 37840 AN: 53392

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

European-Non Finnish (NFE) AF: 0.761 AC: 845875 AN: 1111642

Other (OTH) AF: 0.700 AC: 42240 AN: 60344

GnomAD4 genome AF: 0.695 AC: 105365 AN: 151582 Hom.: 37065 Cov.: 31 AF XY: 0.687 AC XY: 50873 AN XY: 74074

African (AFR) AF: 0.660 AC: 27259 AN: 41318

American (AMR) AF: 0.648 AC: 9876 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2663 AN: 3460

East Asian (EAS) AF: 0.424 AC: 2178 AN: 5142

South Asian (SAS) AF: 0.525 AC: 2525 AN: 4810

European-Finnish (FIN) AF: 0.697 AC: 7320 AN: 10498

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

European-Non Finnish (NFE) AF: 0.754 AC: 51160 AN: 67808

Other (OTH) AF: 0.693 AC: 1456 AN: 2102

Alfa AF: 0.738 Hom.: 68956

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: 81466

Asia WGS AF: 0.459 AC: 1598 AN: 3476

EpiCase AF: 0.758

EpiControl AF: 0.759

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CD52-related disorder Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.9
DANN	Benign	0.85
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	4.3e-7	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.16
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.039
Sift	Benign	1.0	T
Sift4G	Benign	0.93	T
Polyphen		0.0090	B
Vest4		0.021
MPC		0.40
ClinPred		0.0047	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.070
gMVP		0.015
Mutation Taster		=99/1	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: rs1071849; hg19: chr1-26646726; COSMIC: COSV57485050; COSMIC: COSV57485050;