rs2269704

Variant names:

• chr6-30689176-G-A
• rs2269704
• NM_001384369.1:c.507+100C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-30689176-G-A
• chr6-30689176-G-C
• chr6-30689176-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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.: 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

African (AFR) AF: 0.00354 AC: 86 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

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

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: 61 AN: 3472

East Asian (EAS) AF: 0.0433 AC: 224 AN: 5170

South Asian (SAS) AF: 0.0199 AC: 96 AN: 4830

European-Finnish (FIN) AF: 0.00584 AC: 62 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00523 AC: 356 AN: 68010

Other (OTH) AF: 0.0123 AC: 26 AN: 2106

Alfa AF: 0.00702 Hom.: 48

Bravo AF: 0.00780

Asia WGS AF: 0.0250 AC: 88 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
DANN	Benign	0.43
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2269704; hg19: chr6-30656953;