rs2269704

chr6-30689176-G-Achr6-30689176-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRM	NM_001384369.1	c.507+100C>T		intron_variant		ENST00000376421.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRM	ENST00000376421.7	c.507+100C>T		intron_variant		1	NM_001384369.1	P3

Frequencies

GnomAD3 genomes AF: 0.00746 AC: 1135 AN: 152122 Hom.: 15 Cov.: 31

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

Gnomad4 AFR exome AF: 0.00354

Gnomad4 AMR exome AF: 0.00951

Gnomad4 ASJ exome AF: 0.0161

Gnomad4 EAS exome AF: 0.0796

Gnomad4 SAS exome AF: 0.0252

Gnomad4 FIN exome AF: 0.00533

Gnomad4 NFE exome AF: 0.00387

Gnomad4 OTH exome AF: 0.00992

GnomAD4 genome AF: 0.00745 AC: 1134 AN: 152240 Hom.: 16 Cov.: 31 AF XY: 0.00836 AC XY: 622 AN XY: 74424

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.0433

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.00584

Gnomad4 NFE AF: 0.00523

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00715 Hom.: 24

Bravo AF: 0.00780

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.68
Dann	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs2269704; hg19: chr6-30656953;