4-128091365-A-T

Variant names:

• chr4-128091365-A-T
• rs1775865905
• NM_018078.4:c.521A>T

Variant summary

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

The NM_018078.4(LARP1B):​c.521A>T​(p.Tyr174Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y174C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LARP1B NM_018078.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755
• 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: 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 (MetaRNN=0.13522494).

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.521A>T	p.Tyr174Phe	missense	Exon 7 of 20	NP_060548.2
	LARP1B	NM_001410786.1		c.521A>T	p.Tyr174Phe	missense	Exon 7 of 19	NP_001397715.1	A0A994J4X5
	LARP1B	NM_178043.3		c.521A>T	p.Tyr174Phe	missense	Exon 7 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.521A>T	p.Tyr174Phe	missense	Exon 7 of 20	ENSP00000321997.6	Q659C4-1
	LARP1B	ENST00000512292.5	TSL:1	c.521A>T	p.Tyr174Phe	missense	Exon 7 of 12	ENSP00000422850.1	D6R9W6
	LARP1B	ENST00000432347.6	TSL:1	c.521A>T	p.Tyr174Phe	missense	Exon 7 of 9	ENSP00000390395.2	G3V0E9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458218 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725264

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.0000226 AC: 1 AN: 44194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110482

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-0.061
Eigen_PC	Benign	0.028
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.76
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.074
Sift	Benign	0.49	T
Sift4G	Benign	0.41	T
Polyphen		0.021	B
Vest4		0.11
MutPred		0.36		Gain of glycosylation at Y176 (P = 0.0019)
MVP		0.47
MPC		0.14
ClinPred		0.21	T
GERP RS		4.2
Varity_R		0.080
gMVP		0.18
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1775865905; hg19: chr4-129012520;