Genetic Variant ERICH6B:p.Met658Ile (chr13-45541579-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_182542.3(ERICH6B):c.1974G>A(p.Met658Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000869 in 1,551,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 0 hom. )

Consequence

ERICH6B
NM_182542.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0120

Publications

3 publications found

Variant links:

Genes affected

ERICH6B (HGNC:26523): (glutamate rich 6B)

ERICH6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057905912).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182542.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERICH6B	NM_182542.3	MANE Select	c.1974G>A	p.Met658Ile	missense	Exon 15 of 15	NP_872348.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERICH6B	ENST00000298738.3	TSL:2 MANE Select	c.1974G>A	p.Met658Ile	missense	Exon 15 of 15	ENSP00000298738.2	Q5W0A0-1
	ERICH6B	ENST00000504261.5	TSL:3	n.264-6713G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000638

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000521

AC:

AN:

157350

AF XY:

0.000588

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000688

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000950

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.000894

AC:

1251

AN:

1399640

Hom.:

Cov.:

AF XY:

0.000888

AC XY:

613

AN XY:

690324

show subpopulations

African (AFR)

AF:

0.000253

AC:

AN:

31598

American (AMR)

AF:

0.000644

AC:

AN:

35706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00108

AC:

1165

AN:

1079022

Other (OTH)

AF:

0.000930

AC:

AN:

58050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

148

223

297

371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

144

192

240

<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:

0.000637

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41548

American (AMR)

AF:

0.00190

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68022

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000638

Hom.:

Bravo

AF:

0.000604

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000158

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.2

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.0037

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.43

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

PhyloP100

-0.012

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.69

REVEL

Benign

0.027

Sift

Benign

0.049

Sift4G

Benign

0.11

Polyphen

0.52

Vest4

0.20

MutPred

0.39

Loss of MoRF binding (P = 0.1185)

MVP

0.030

ClinPred

0.019

GERP RS

2.8

Varity_R

0.18

gMVP

0.14

Mutation Taster

=93/7

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over