rs754272530

Variant names:

• chr2-151493859-G-A
• rs754272530
• NM_001164507.2:c.24588C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-151493859-G-A
• chr2-151493859-G-C
• chr2-151493859-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164507.2(NEB):​c.24588C>T​(p.Tyr8196Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000142 in 1,405,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NEB NM_001164507.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.26
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEB	NM_001164507.2	c.24588C>T	p.Tyr8196Tyr	synonymous_variant	Exon 175 of 182	ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2	c.24588C>T	p.Tyr8196Tyr	synonymous_variant	Exon 175 of 182	ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEB	ENST00000397345.8	c.24588C>T	p.Tyr8196Tyr	synonymous_variant	Exon 175 of 182	5	NM_001164508.2	ENSP00000380505.3
NEB	ENST00000427231.7	c.24588C>T	p.Tyr8196Tyr	synonymous_variant	Exon 175 of 182	5	NM_001164507.2	ENSP00000416578.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1405200 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 694806

African (AFR) AF: 0.00 AC: 0 AN: 31764

American (AMR) AF: 0.00 AC: 0 AN: 35862

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24944

East Asian (EAS) AF: 0.00 AC: 0 AN: 38396

South Asian (SAS) AF: 0.00 AC: 0 AN: 77954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1081244

Other (OTH) AF: 0.00 AC: 0 AN: 58294

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.0
DANN	Benign	0.83
PhyloP100		6.3
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs754272530; hg19: chr2-152350373;