4-128098189-A-G

Variant names:

• chr4-128098189-A-G
• rs745589559
• NM_018078.4:c.672A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018078.4(LARP1B):​c.672A>G​(p.Glu224Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,332 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: LARP1B NM_018078.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.821
• Publications: 0 publications found

Genes affected

LARP1B (HGNC:24704): (La ribonucleoprotein 1B) This gene encodes a protein containing domains found in the La related protein of Drosophila melanogaster. La motif-containing proteins are thought to be RNA-binding proteins, where the La motif and adjacent amino acids fold into an RNA recognition motif. The La motif is also found in proteins unrelated to the La protein. Alternative splicing has been observed at this locus and multiple variants, encoding distinct isoforms, are described. Additional splice variation has been identified but the full-length nature of these transcripts has not been determined. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.04).
• BP7: Synonymous conserved (PhyloP=0.821 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018078.4. 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
	LARP1B	NM_018078.4	MANE Select	c.672A>G	p.Glu224Glu	synonymous	Exon 8 of 20	NP_060548.2
	LARP1B	NM_001410786.1		c.672A>G	p.Glu224Glu	synonymous	Exon 8 of 19	NP_001397715.1	A0A994J4X5
	LARP1B	NM_178043.3		c.672A>G	p.Glu224Glu	synonymous	Exon 8 of 11	NP_835144.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP1B	ENST00000326639.11	TSL:5 MANE Select	c.672A>G	p.Glu224Glu	synonymous	Exon 8 of 20	ENSP00000321997.6	Q659C4-1
	LARP1B	ENST00000512292.5	TSL:1	c.672A>G	p.Glu224Glu	synonymous	Exon 8 of 12	ENSP00000422850.1	D6R9W6
	LARP1B	ENST00000432347.6	TSL:1	c.672A>G	p.Glu224Glu	synonymous	Exon 8 of 9	ENSP00000390395.2	G3V0E9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453332 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 723456

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 85946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104498

Other (OTH) AF: 0.0000166 AC: 1 AN: 60160

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.5
DANN	Benign	0.49
PhyloP100		0.82

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: rs745589559; hg19: chr4-129019344;