dbSNP rs8587: EMC8:c.*83T>G (chr16-85779625-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_006067.5(EMC8):c.*83T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,409,332 control chromosomes in the GnomAD database, including 403,836 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 0.68 ( 36760 hom., cov: 32)

Exomes 𝑓: 0.75 ( 367076 hom. )

Consequence

EMC8
NM_006067.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.201

Publications

19 publications found

Variant links:

Genes affected

EMC8 (HGNC:7864): (ER membrane protein complex subunit 8) Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Located in cytosol. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

EMC8 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 (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EMC8	NM_006067.5 link	c.*83T>G	3_prime_UTR_variant	Exon 5 of 5	ENST00000253457.8	NP_006058.1	O43402-1Q53Y03
EMC8	NM_001142288.2 link	c.*240T>G	3_prime_UTR_variant	Exon 4 of 4		NP_001135760.1	O43402-2
EMC8	XM_017022867.2 link	c.*83T>G	3_prime_UTR_variant	Exon 6 of 6		XP_016878356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMC8	ENST00000253457.8 link	c.*83T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_006067.5	ENSP00000253457.3		O43402-1

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

103426

AN:

151918

Hom.:

36750

Cov.:

show subpopulations

Gnomad AFR

AF:

0.544

Gnomad AMI

AF:

0.848

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.828

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.792

Gnomad OTH

AF:

0.711

GnomAD4 exome

AF:

0.754

AC:

947824

AN:

1257296

Hom.:

367076

Cov.:

AF XY:

0.755

AC XY:

475893

AN XY:

630706

show subpopulations

African (AFR)

AF:

0.541

AC:

15905

AN:

29402

American (AMR)

AF:

0.489

AC:

20838

AN:

42642

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

16854

AN:

23474

East Asian (EAS)

AF:

0.229

AC:

8768

AN:

38256

South Asian (SAS)

AF:

0.691

AC:

54721

AN:

79162

European-Finnish (FIN)

AF:

0.822

AC:

40728

AN:

49576

Middle Eastern (MID)

AF:

0.781

AC:

3870

AN:

4958

European-Non Finnish (NFE)

AF:

0.798

AC:

747263

AN:

936432

Other (OTH)

AF:

0.728

AC:

38877

AN:

53394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

10358

20716

31073

41431

51789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16434

32868

49302

65736

82170

<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:

0.681

AC:

103468

AN:

152036

Hom.:

36760

Cov.:

AF XY:

0.678

AC XY:

50383

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.544

AC:

22532

AN:

41424

American (AMR)

AF:

0.578

AC:

8835

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.723

AC:

2505

AN:

3466

East Asian (EAS)

AF:

0.223

AC:

1153

AN:

5160

South Asian (SAS)

AF:

0.688

AC:

3321

AN:

4824

European-Finnish (FIN)

AF:

0.828

AC:

8760

AN:

10576

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.792

AC:

53856

AN:

67980

Other (OTH)

AF:

0.713

AC:

1508

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1564

3129

4693

6258

7822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.746

Hom.:

135904

Bravo

AF:

0.651

Asia WGS

AF:

0.478

AC:

1662

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.94

(source)

DANN

Benign

0.65

PhyloP100

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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