rs2532502

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001242.5(CD27):c.698A>G(p.His233Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,614,090 control chromosomes in the GnomAD database, including 792,098 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 75172 hom., cov: 31)

Exomes 𝑓: 0.99 ( 716926 hom. )

Consequence

CD27
NM_001242.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.374

Variant links:

Genes affected

CD27 (HGNC:11922): (CD27 molecule) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is required for generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis. This receptor transduces signals that lead to the activation of NF-kappaB and MAPK8/JNK. Adaptor proteins TRAF2 and TRAF5 have been shown to mediate the signaling process of this receptor. CD27-binding protein (SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the apoptosis induced by this receptor. [provided by RefSeq, Jul 2008]

CD27 links:

CD27-AS1 (HGNC:43896): (CD27 antisense RNA 1)

CD27-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.73214E-7).

BP6

Variant 12-6451307-A-G is Benign according to our data. Variant chr12-6451307-A-G is described in ClinVar as [Benign]. Clinvar id is 402517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD27	NM_001242.5 linkuse as main transcript	c.698A>G	p.His233Arg	missense_variant	6/6	ENST00000266557.4
CD27-AS1	NR_015382.2 linkuse as main transcript	n.211T>C		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD27	ENST00000266557.4 linkuse as main transcript	c.698A>G	p.His233Arg	missense_variant	6/6	1	NM_001242.5	P1
CD27-AS1	ENST00000689782.1 linkuse as main transcript	n.100+162T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.994

AC:

151187

AN:

152162

Hom.:

75112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.996

Gnomad ASJ

AF:

0.988

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.995

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.989

Gnomad OTH

AF:

0.993

GnomAD3 exomes

AF:

0.993

AC:

249087

AN:

250914

Hom.:

123640

AF XY:

0.992

AC XY:

134623

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.998

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

0.986

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.994

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.989

Gnomad OTH exome

AF:

0.991

GnomAD4 exome

AF:

0.990

AC:

1447750

AN:

1461810

Hom.:

716926

Cov.:

AF XY:

0.990

AC XY:

720213

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.998

Gnomad4 AMR exome

AF:

0.997

Gnomad4 ASJ exome

AF:

0.986

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.994

Gnomad4 FIN exome

AF:

0.999

Gnomad4 NFE exome

AF:

0.989

Gnomad4 OTH exome

AF:

0.992

GnomAD4 genome

AF:

0.994

AC:

151306

AN:

152280

Hom.:

75172

Cov.:

AF XY:

0.994

AC XY:

74012

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.998

Gnomad4 AMR

AF:

0.996

Gnomad4 ASJ

AF:

0.988

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.995

Gnomad4 FIN

AF:

0.998

Gnomad4 NFE

AF:

0.989

Gnomad4 OTH

AF:

0.993

Alfa

AF:

0.989

Hom.:

107579

Bravo

AF:

0.993

TwinsUK

AF:

0.989

AC:

3666

ALSPAC

AF:

0.990

AC:

3815

ESP6500AA

AF:

0.996

AC:

4390

ESP6500EA

AF:

0.989

AC:

8508

ExAC

AF:

0.993

AC:

120514

Asia WGS

AF:

0.998

AC:

3469

AN:

3476

EpiCase

AF:

0.988

EpiControl

AF:

0.989

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 02, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 96. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Lymphoproliferative syndrome 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.21

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.12

MetaRNN

Benign

6.7e-7

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

0.15

REVEL

Benign

0.25

Sift

Benign

0.17

Sift4G

Uncertain

0.027

Polyphen

0.0

Vest4

0.010

MPC

0.23

ClinPred

0.0064

GERP RS

1.9

Varity_R

0.050

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over