rs56026241

Variant names:

• chr2-151531901-AT-A
• rs56026241
• NM_001164507.2:c.21418-6delA

Your query was ambiguous. Multiple possible variants found:

• chr2-151531901-AT-A
• chr2-151531901-AT-ATT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001164508.2(NEB):​c.21418-6delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24355 hom., cov: 0)
  • Exomes 𝑓: 0.61 (264503 hom.)
• Consequence: NEB NM_001164508.2 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 2.54
• Publications: 7 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 -16 ACMG points.

• BP6: Variant 2-151531901-AT-A is Benign according to our data. Variant chr2-151531901-AT-A is described in ClinVar as Benign. ClinVar VariationId is 95112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.671 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.21418-6delA		splice_region intron	N/A	NP_001157979.2	P20929-3
	NEB	NM_001164508.2	MANE Select	c.21418-6delA		splice_region intron	N/A	NP_001157980.2	P20929-2
	NEB	NM_001271208.2		c.21523-6delA		splice_region intron	N/A	NP_001258137.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEB	ENST00000397345.8	TSL:5 MANE Select	c.21418-6delA		splice_region intron	N/A	ENSP00000380505.3	P20929-2
	NEB	ENST00000427231.7	TSL:5 MANE Plus Clinical	c.21418-6delA		splice_region intron	N/A	ENSP00000416578.2	P20929-3
	NEB	ENST00000409198.5	TSL:5	c.16315-6delA		splice_region intron	N/A	ENSP00000386259.1	P20929-4

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84079 AN: 151834 Hom.: 24334 Cov.: 0

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.565

GnomAD2 exomes AF: 0.591 AC: 127200 AN: 215382 AF XY: 0.581

Gnomad AFR exome AF: 0.388

Gnomad AMR exome AF: 0.724

Gnomad ASJ exome AF: 0.526

Gnomad EAS exome AF: 0.583

Gnomad FIN exome AF: 0.639

Gnomad NFE exome AF: 0.624

Gnomad OTH exome AF: 0.610

GnomAD4 exome AF: 0.607 AC: 858614 AN: 1414682 Hom.: 264503 Cov.: 0 AF XY: 0.601 AC XY: 422334 AN XY: 702968

African (AFR) AF: 0.382 AC: 12515 AN: 32740

American (AMR) AF: 0.713 AC: 29398 AN: 41250

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 13247 AN: 25492

East Asian (EAS) AF: 0.627 AC: 24513 AN: 39116

South Asian (SAS) AF: 0.410 AC: 33721 AN: 82282

European-Finnish (FIN) AF: 0.640 AC: 33386 AN: 52178

Middle Eastern (MID) AF: 0.601 AC: 3423 AN: 5692

European-Non Finnish (NFE) AF: 0.625 AC: 673736 AN: 1077122

Other (OTH) AF: 0.590 AC: 34675 AN: 58810

GnomAD4 genome AF: 0.554 AC: 84129 AN: 151952 Hom.: 24355 Cov.: 0 AF XY: 0.556 AC XY: 41269 AN XY: 74260

African (AFR) AF: 0.385 AC: 15938 AN: 41438

American (AMR) AF: 0.681 AC: 10418 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1770 AN: 3468

East Asian (EAS) AF: 0.581 AC: 3002 AN: 5164

South Asian (SAS) AF: 0.404 AC: 1939 AN: 4804

European-Finnish (FIN) AF: 0.644 AC: 6793 AN: 10556

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42440 AN: 67920

Other (OTH) AF: 0.558 AC: 1178 AN: 2110

Alfa AF: 0.593 Hom.: 4866

Bravo AF: 0.554

Asia WGS AF: 0.450 AC: 1568 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Nemaline myopathy 2 (2)
-	-	2	not provided (2)
-	-	1	Nemaline Myopathy, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56026241; hg19: chr2-152388415;