Variant rs2250145 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_206966.3(C5orf46):c.11C>T(p.Ser4Leu) variant causes a missense change. The variant allele was found at a frequency of 0.567 in 1,605,674 control chromosomes in the GnomAD database, including 264,490 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 0.48 ( 19592 hom., cov: 32)

Exomes 𝑓: 0.58 ( 244898 hom. )

Consequence

C5orf46
NM_206966.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.24

Variant links:

Genes affected

C5orf46 (HGNC:33768): (chromosome 5 open reading frame 46) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

C5orf46 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6146898E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
C5orf46	NM_206966.3 linkuse as main transcript	c.11C>T	p.Ser4Leu	missense_variant	1/4	ENST00000318315.5	NP_996849.2
C5orf46	XM_005268446.4 linkuse as main transcript	c.11C>T	p.Ser4Leu	missense_variant	1/4		XP_005268503.3
C5orf46	XM_047417169.1 linkuse as main transcript	c.11C>T	p.Ser4Leu	missense_variant	1/3		XP_047273125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5orf46	ENST00000318315.5 linkuse as main transcript	c.11C>T	p.Ser4Leu	missense_variant	1/4	1	NM_206966.3	ENSP00000315370	P1	Q6UWT4-1
C5orf46	ENST00000515291.1 linkuse as main transcript	c.11C>T	p.Ser4Leu	missense_variant	1/2	1		ENSP00000425984		Q6UWT4-2
C5orf46	ENST00000510432.1 linkuse as main transcript			upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

72973

AN:

151832

Hom.:

19599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.587

Gnomad OTH

AF:

0.502

GnomAD3 exomes

AF:

0.557

AC:

138793

AN:

249138

Hom.:

40240

AF XY:

0.569

AC XY:

76583

AN XY:

134574

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.454

Gnomad ASJ exome

AF:

0.556

Gnomad EAS exome

AF:

0.617

Gnomad SAS exome

AF:

0.612

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.592

Gnomad OTH exome

AF:

0.556

GnomAD4 exome

AF:

0.576

AC:

837181

AN:

1453724

Hom.:

244898

Cov.:

AF XY:

0.579

AC XY:

418608

AN XY:

723140

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.458

Gnomad4 ASJ exome

AF:

0.551

Gnomad4 EAS exome

AF:

0.597

Gnomad4 SAS exome

AF:

0.611

Gnomad4 FIN exome

AF:

0.651

Gnomad4 NFE exome

AF:

0.586

Gnomad4 OTH exome

AF:

0.556

GnomAD4 genome

AF:

0.480

AC:

72970

AN:

151950

Hom.:

19592

Cov.:

AF XY:

0.484

AC XY:

35972

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.473

Gnomad4 ASJ

AF:

0.536

Gnomad4 EAS

AF:

0.602

Gnomad4 SAS

AF:

0.599

Gnomad4 FIN

AF:

0.660

Gnomad4 NFE

AF:

0.587

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.566

Hom.:

63439

Bravo

AF:

0.459

TwinsUK

AF:

0.583

AC:

2161

ALSPAC

AF:

0.573

AC:

2207

ESP6500AA

AF:

0.227

AC:

1001

ESP6500EA

AF:

0.585

AC:

5030

ExAC

AF:

0.557

AC:

67606

Asia WGS

AF:

0.510

AC:

1773

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.00016

T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

0.38

P;P

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Benign

0.21

Sift

Benign

0.12

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.45

MPC

0.18

ClinPred

0.027

GERP RS

4.9

Varity_R

0.32

gMVP

0.31

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over