rs1057519297

Variant names:

• chr4-112646356-GAT-G
• rs1057519297
• NM_016648.4:c.213_214delAT

Your query was ambiguous. Multiple possible variants found:

• chr4-112646356-GAT-G
• chr4-112646356-GAT-GATAT

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_016648.4(LARP7):​c.213_214delAT​(p.Ser72ThrfsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000786 in 1,272,546 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: LARP7 NM_016648.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.65
• Publications: 0 publications found

Genes affected

LARP7 (HGNC:24912): (La ribonucleoprotein 7, transcriptional regulator) This gene encodes a protein which is found in the 7SK snRNP (small nuclear ribonucleoprotein). This snRNP complex inhibits a cyclin-dependent kinase, positive transcription elongation factor b, which is required for paused RNA polymerase II at a promoter to begin transcription elongation. A pseudogene of this gene is located on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

MIR302CHG (HGNC:41070): (miR-302/367 cluster host gene)

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016648.4. 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
	LARP7	NM_016648.4	MANE Select	c.213_214delAT	p.Ser72ThrfsTer6	frameshift	Exon 3 of 13	NP_057732.2
	LARP7	NM_001370974.1		c.213_214delAT	p.Ser72ThrfsTer6	frameshift	Exon 3 of 13	NP_001357903.1
	LARP7	NM_001370975.1		c.213_214delAT	p.Ser72ThrfsTer6	frameshift	Exon 3 of 13	NP_001357904.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP7	ENST00000344442.10	TSL:2 MANE Select	c.213_214delAT	p.Ser72ThrfsTer6	frameshift	Exon 3 of 13	ENSP00000344950.5
	LARP7	ENST00000509061.5	TSL:1	c.213_214delAT	p.Ser72ThrfsTer6	frameshift	Exon 5 of 15	ENSP00000422626.2
	LARP7	ENST00000509622.5	TSL:1	n.110_111delAT		non_coding_transcript_exon	Exon 3 of 13	ENSP00000422451.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.86e-7 AC: 1 AN: 1272546 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 642222

African (AFR) AF: 0.00 AC: 0 AN: 29030

American (AMR) AF: 0.00 AC: 0 AN: 41040

Ashkenazi Jewish (ASJ) AF: 0.0000408 AC: 1 AN: 24480

East Asian (EAS) AF: 0.00 AC: 0 AN: 38336

South Asian (SAS) AF: 0.00 AC: 0 AN: 79494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4864

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 948388

Other (OTH) AF: 0.00 AC: 0 AN: 53958

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.7

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: rs1057519297; hg19: chr4-113567512;