rs149510427

Variant names:

• chr2-151531078-G-A
• rs149510427
• NM_001164507.2:c.21546C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-151531078-G-A
• chr2-151531078-G-C
• chr2-151531078-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001164508.2(NEB):​c.21546C>T​(p.Asn7182Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00651 in 1,611,652 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0078 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (276 hom.)
• Consequence: NEB NM_001164508.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 6.51
• Publications: 4 publications found

Genes affected

NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]

RIF1 (HGNC:23207): (replication timing regulatory factor 1) This gene encodes a protein that shares homology with the yeast teleomere binding protein, Rap1 interacting factor 1. This protein localizes to aberrant telomeres may be involved in DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 2-151531078-G-A is Benign according to our data. Variant chr2-151531078-G-A is described in ClinVar as Benign. ClinVar VariationId is 95113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164508.2. 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
	NEB	NM_001164507.2	MANE Plus Clinical	c.21546C>T	p.Asn7182Asn	synonymous	Exon 145 of 182	NP_001157979.2	P20929-3
	NEB	NM_001164508.2	MANE Select	c.21546C>T	p.Asn7182Asn	synonymous	Exon 145 of 182	NP_001157980.2	P20929-2
	NEB	NM_001271208.2		c.21651C>T	p.Asn7217Asn	synonymous	Exon 146 of 183	NP_001258137.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEB	ENST00000397345.8	TSL:5 MANE Select	c.21546C>T	p.Asn7182Asn	synonymous	Exon 145 of 182	ENSP00000380505.3	P20929-2
	NEB	ENST00000427231.7	TSL:5 MANE Plus Clinical	c.21546C>T	p.Asn7182Asn	synonymous	Exon 145 of 182	ENSP00000416578.2	P20929-3
	NEB	ENST00000409198.5	TSL:5	c.16443C>T	p.Asn5481Asn	synonymous	Exon 118 of 150	ENSP00000386259.1	P20929-4

Frequencies

GnomAD3 genomes AF: 0.00782 AC: 1190 AN: 152078 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.0160 AC: 3950 AN: 247620 AF XY: 0.0136

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.0605

Gnomad ASJ exome AF: 0.0145

Gnomad EAS exome AF: 0.0630

Gnomad FIN exome AF: 0.0107

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.0116

GnomAD4 exome AF: 0.00637 AC: 9293 AN: 1459456 Hom.: 276 Cov.: 31 AF XY: 0.00610 AC XY: 4428 AN XY: 726044

African (AFR) AF: 0.000687 AC: 23 AN: 33456

American (AMR) AF: 0.0578 AC: 2576 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.0143 AC: 374 AN: 26106

East Asian (EAS) AF: 0.0898 AC: 3559 AN: 39618

South Asian (SAS) AF: 0.00308 AC: 265 AN: 85948

European-Finnish (FIN) AF: 0.0114 AC: 608 AN: 53374

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.00130 AC: 1446 AN: 1110328

Other (OTH) AF: 0.00720 AC: 434 AN: 60280

GnomAD4 genome AF: 0.00785 AC: 1194 AN: 152196 Hom.: 30 Cov.: 32 AF XY: 0.00895 AC XY: 666 AN XY: 74412

African (AFR) AF: 0.000626 AC: 26 AN: 41526

American (AMR) AF: 0.0318 AC: 486 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3472

East Asian (EAS) AF: 0.0708 AC: 367 AN: 5182

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4818

European-Finnish (FIN) AF: 0.0116 AC: 123 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00156 AC: 106 AN: 67998

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00282 Hom.: 1

Bravo AF: 0.0103

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	Nemaline myopathy 2 (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.4
DANN	Benign	0.74
PhyloP100		6.5
Mutation Taster		=48/52	polymorphism (auto)

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: rs149510427; hg19: chr2-152387592; COSMIC: COSV51420235; COSMIC: COSV51420235;