dbSNP rs510579: C6orf118:p.Ile256Met (chr6-165300472-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144980.4(C6orf118):c.768T>G(p.Ile256Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,607,492 control chromosomes in the GnomAD database, including 121,026 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 ( 19750 hom., cov: 32)

Exomes 𝑓: 0.36 ( 101276 hom. )

Consequence

C6orf118
NM_144980.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

Publications

21 publications found

Variant links:

Genes affected

C6orf118 (HGNC:21233): (chromosome 6 open reading frame 118)

C6orf118 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6664145E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6orf118	NM_144980.4 link	c.768T>G	p.Ile256Met	missense_variant	Exon 3 of 9	ENST00000230301.9	NP_659417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C6orf118	ENST00000230301.9 link	c.768T>G	p.Ile256Met	missense_variant	Exon 3 of 9	1	NM_144980.4	ENSP00000230301.8

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72513

AN:

151906

Hom.:

19695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.429

GnomAD2 exomes

AF:

0.390

AC:

96856

AN:

248658

AF XY:

0.383

show subpopulations

Gnomad AFR exome

AF:

0.758

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.474

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.364

AC:

530410

AN:

1455468

Hom.:

101276

Cov.:

AF XY:

0.365

AC XY:

264291

AN XY:

724228

show subpopulations

African (AFR)

AF:

0.772

AC:

25625

AN:

33212

American (AMR)

AF:

0.375

AC:

16626

AN:

44330

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

9466

AN:

26024

East Asian (EAS)

AF:

0.252

AC:

10001

AN:

39630

South Asian (SAS)

AF:

0.401

AC:

34453

AN:

85820

European-Finnish (FIN)

AF:

0.471

AC:

24825

AN:

52670

Middle Eastern (MID)

AF:

0.380

AC:

2180

AN:

5734

European-Non Finnish (NFE)

AF:

0.347

AC:

384239

AN:

1107948

Other (OTH)

AF:

0.383

AC:

22995

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

15866

31733

47599

63466

79332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12356

24712

37068

49424

61780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.478

AC:

72623

AN:

152024

Hom.:

19750

Cov.:

AF XY:

0.482

AC XY:

35777

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.751

AC:

31138

AN:

41480

American (AMR)

AF:

0.413

AC:

6306

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1267

AN:

3470

East Asian (EAS)

AF:

0.224

AC:

1154

AN:

5162

South Asian (SAS)

AF:

0.419

AC:

2016

AN:

4808

European-Finnish (FIN)

AF:

0.474

AC:

5004

AN:

10564

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24370

AN:

67960

Other (OTH)

AF:

0.429

AC:

906

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1702

3403

5105

6806

8508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.390

Hom.:

37238

Bravo

AF:

0.477

TwinsUK

AF:

0.347

AC:

1285

ALSPAC

AF:

0.337

AC:

1299

ESP6500AA

AF:

0.747

AC:

3290

ESP6500EA

AF:

0.349

AC:

2999

ExAC

AF:

0.396

AC:

48013

Asia WGS

AF:

0.359

AC:

1248

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.057

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0080

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0000017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

-2.0

PROVEAN

Benign

-1.1

REVEL

Benign

0.090

Sift

Benign

0.14

Sift4G

Benign

0.10

Polyphen

0.99

Vest4

0.059

MPC

0.074

ClinPred

0.035

GERP RS

-10

Varity_R

0.055

gMVP

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over