chr4-128103118-C-T

Variant names:

• chr4-128103118-C-T
• rs4834232
• NM_018078.4:c.814-4021C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018078.4(LARP1B):​c.814-4021C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,076 control chromosomes in the GnomAD database, including 2,889 homozygotes. 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: 𝑓 0.18 (2889 hom., cov: 32)
• Consequence: LARP1B NM_018078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

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.814-4021C>T		intron	N/A	NP_060548.2
	LARP1B	NM_001410786.1		c.814-4021C>T		intron	N/A	NP_001397715.1	A0A994J4X5
	LARP1B	NM_001350531.2		c.91-4021C>T		intron	N/A	NP_001337460.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP1B	ENST00000326639.11	TSL:5 MANE Select	c.814-4021C>T		intron	N/A	ENSP00000321997.6	Q659C4-1
	LARP1B	ENST00000512292.5	TSL:1	c.814-4021C>T		intron	N/A	ENSP00000422850.1	D6R9W6
	LARP1B	ENST00000432347.6	TSL:1	c.814-4021C>T		intron	N/A	ENSP00000390395.2	G3V0E9

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26890 AN: 151958 Hom.: 2887 Cov.: 32

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.210

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.177 AC: 26910 AN: 152076 Hom.: 2889 Cov.: 32 AF XY: 0.179 AC XY: 13313 AN XY: 74342

African (AFR) AF: 0.0677 AC: 2812 AN: 41524

American (AMR) AF: 0.228 AC: 3468 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3468

East Asian (EAS) AF: 0.140 AC: 723 AN: 5176

South Asian (SAS) AF: 0.285 AC: 1370 AN: 4814

European-Finnish (FIN) AF: 0.194 AC: 2051 AN: 10572

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14858 AN: 67968

Other (OTH) AF: 0.213 AC: 450 AN: 2110

Alfa AF: 0.210 Hom.: 15782

Bravo AF: 0.172

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.24
DANN	Benign	0.56
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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: rs4834232; hg19: chr4-129024273;