Genetic Variant NRM:c.507+100C>T (chr6-30689176-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_001384369.1(NRM):c.507+100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00806 in 1,256,122 control chromosomes in the GnomAD database, including 257 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 0.0074 ( 16 hom., cov: 31)

Exomes 𝑓: 0.0081 ( 241 hom. )

Consequence

NRM
NM_001384369.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.427

Publications

12 publications found

Variant links:

Genes affected

NRM (HGNC:8003): (nurim) The protein encoded by this gene contains transmembrane domains and resides within the inner nuclear membrane, where it is tightly associated with the nucleus. This protein shares homology with isoprenylcysteine carboxymethyltransferase enzymes. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

NRM links:

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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=-0.89).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384369.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NRM	NM_001384369.1	MANE Select	c.507+100C>T	intron	N/A	NP_001371298.1
NRM	NM_001270707.2		c.525+100C>T	intron	N/A	NP_001257636.1
NRM	NM_007243.3		c.507+100C>T	intron	N/A	NP_009174.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NRM	ENST00000376421.7	TSL:1 MANE Select	c.507+100C>T	intron	N/A	ENSP00000365603.5
NRM	ENST00000376420.9	TSL:1	c.331-234C>T	intron	N/A	ENSP00000365602.5
NRM	ENST00000474864.5	TSL:1	n.134-234C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00746

AC:

1135

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.0432

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00523

Gnomad OTH

AF:

0.0130

GnomAD4 exome

AF:

0.00814

AC:

8988

AN:

1103882

Hom.:

241

AF XY:

0.00876

AC XY:

4783

AN XY:

546044

show subpopulations

African (AFR)

AF:

0.00354

AC:

AN:

24270

American (AMR)

AF:

0.00951

AC:

221

AN:

23236

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

296

AN:

18338

East Asian (EAS)

AF:

0.0796

AC:

2720

AN:

34172

South Asian (SAS)

AF:

0.0252

AC:

1534

AN:

60920

European-Finnish (FIN)

AF:

0.00533

AC:

225

AN:

42218

Middle Eastern (MID)

AF:

0.0338

AC:

154

AN:

4562

European-Non Finnish (NFE)

AF:

0.00387

AC:

3281

AN:

848696

Other (OTH)

AF:

0.00992

AC:

471

AN:

47470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

481

962

1442

1923

2404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<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:

0.00745

AC:

1134

AN:

152240

Hom.:

Cov.:

AF XY:

0.00836

AC XY:

622

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00289

AC:

120

AN:

41542

American (AMR)

AF:

0.0111

AC:

170

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3472

East Asian (EAS)

AF:

0.0433

AC:

224

AN:

5170

South Asian (SAS)

AF:

0.0199

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00584

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00523

AC:

356

AN:

68010

Other (OTH)

AF:

0.0123

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00702

Hom.:

Bravo

AF:

0.00780

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.68

(source)

DANN

Benign

0.43

PhyloP100

-0.43

Mutation Taster

=100/0

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