rs1775865905

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-128091365-A-G
• chr4-128091365-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018078.4(LARP1B):​c.521A>G​(p.Tyr174Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LARP1B NM_018078.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39610317).

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>G	p.Tyr174Cys	missense	Exon 7 of 20	NP_060548.2
	LARP1B	NM_001410786.1		c.521A>G	p.Tyr174Cys	missense	Exon 7 of 19	NP_001397715.1	A0A994J4X5
	LARP1B	NM_178043.3		c.521A>G	p.Tyr174Cys	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>G	p.Tyr174Cys	missense	Exon 7 of 20	ENSP00000321997.6	Q659C4-1
	LARP1B	ENST00000512292.5	TSL:1	c.521A>G	p.Tyr174Cys	missense	Exon 7 of 12	ENSP00000422850.1	D6R9W6
	LARP1B	ENST00000432347.6	TSL:1	c.521A>G	p.Tyr174Cys	missense	Exon 7 of 9	ENSP00000390395.2	G3V0E9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458218 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725264

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

American (AMR) AF: 0.00 AC: 0 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: 0.00000270 AC: 3 AN: 1110482

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.76
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.18
Sift	Benign	0.058	T
Sift4G	Benign	0.088	T
Polyphen		1.0	D
Vest4		0.15
MutPred		0.38		Gain of glycosylation at Y176 (P = 0.0019)
MVP		0.56
MPC		0.20
ClinPred		0.83	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.37
Mutation Taster		=61/39	polymorphism

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: rs1775865905; hg19: chr4-129012520; COSMIC: COSV99218644;