rs2049714734

Variant names:

• chr2-151485665-C-G
• rs2049714734
• NM_001164507.2:c.*95G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-151485665-C-G
• chr2-151485665-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001164508.2(NEB):​c.*95G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000938 in 1,066,150 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: 33)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: NEB NM_001164508.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.*95G>C		3_prime_UTR	Exon 182 of 182	NP_001157979.2	P20929-3
	NEB	NM_001164508.2	MANE Select	c.*95G>C		3_prime_UTR	Exon 182 of 182	NP_001157980.2	P20929-2
	NEB	NM_001271208.2		c.*95G>C		3_prime_UTR	Exon 183 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.*95G>C		3_prime_UTR	Exon 182 of 182	ENSP00000380505.3	P20929-2
	NEB	ENST00000427231.7	TSL:5 MANE Plus Clinical	c.*95G>C		3_prime_UTR	Exon 182 of 182	ENSP00000416578.2	P20929-3
	NEB	ENST00000409198.5	TSL:5	c.*95G>C		3_prime_UTR	Exon 150 of 150	ENSP00000386259.1	P20929-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.38e-7 AC: 1 AN: 1066150 Hom.: 0 Cov.: 13 AF XY: 0.00000189 AC XY: 1 AN XY: 528792

African (AFR) AF: 0.00 AC: 0 AN: 24734

American (AMR) AF: 0.00 AC: 0 AN: 27432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17584

East Asian (EAS) AF: 0.00 AC: 0 AN: 36856

South Asian (SAS) AF: 0.0000187 AC: 1 AN: 53500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3214

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 817228

Other (OTH) AF: 0.00 AC: 0 AN: 46250

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.58
PhyloP100		0.66

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: rs2049714734; hg19: chr2-152342179;