dbSNP rs8962: NEMP2:c.*2266C>T (chr2-190506923-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001142645.2(NEMP2):c.*2266C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,102 control chromosomes in the GnomAD database, including 1,839 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 0.15 ( 1838 hom., cov: 32)

Exomes 𝑓: 0.27 ( 1 hom. )

Consequence

NEMP2
NM_001142645.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.301

Publications

2 publications found

Variant links:

Genes affected

NEMP2 (HGNC:33700): (nuclear envelope integral membrane protein 2) Predicted to be located in nuclear inner membrane. Predicted to be integral component of membrane. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

NEMP2 links:

MFSD6 (HGNC:24711): (major facilitator superfamily domain containing 6) Predicted to enable MHC class I protein binding activity and MHC class I receptor activity. Predicted to be involved in antigen processing and presentation of exogenous peptide antigen via MHC class I. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD6 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142645.2. 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
	NEMP2	NM_001142645.2	MANE Select	c.*2266C>T		3_prime_UTR	Exon 9 of 9	NP_001136117.1	A6NFY4-1
	NEMP2	NR_136298.2		n.3541C>T		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEMP2	ENST00000409150.8	TSL:2 MANE Select	c.*2266C>T		3_prime_UTR	Exon 9 of 9	ENSP00000386292.3	A6NFY4-1
	MFSD6	ENST00000412482.1	TSL:3	n.*184+1802G>A		intron	N/A	ENSP00000404511.1	H7C284

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22231

AN:

151962

Hom.:

1837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0750

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.163

GnomAD4 exome

AF:

0.273

AC:

AN:

Hom.:

Cov.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0833

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.146

AC:

22233

AN:

152080

Hom.:

1838

Cov.:

AF XY:

0.144

AC XY:

10673

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0750

AC:

3110

AN:

41494

American (AMR)

AF:

0.140

AC:

2146

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

851

AN:

3464

East Asian (EAS)

AF:

0.147

AC:

760

AN:

5164

South Asian (SAS)

AF:

0.162

AC:

783

AN:

4824

European-Finnish (FIN)

AF:

0.115

AC:

1215

AN:

10566

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12797

AN:

67966

Other (OTH)

AF:

0.161

AC:

339

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

947

1893

2840

3786

4733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.164

Hom.:

882

Bravo

AF:

0.144

Asia WGS

AF:

0.122

AC:

424

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

8.7

(source)

DANN

Benign

0.48

PhyloP100

0.30

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over