10-810978-A-T

Variant names:

• chr10-810978-A-T
• rs4229
• NM_015155.3:c.*1948T>A

Variant summary

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

The NM_015155.3(LARP4B):​c.*1948T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,118 control chromosomes in the GnomAD database, including 13,307 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 0.41 (13305 hom., cov: 33)
  • Exomes 𝑓: 0.83 (2 hom.)
• Consequence: LARP4B NM_015155.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.880
• Publications: 10 publications found

Genes affected

LARP4B (HGNC:28987): (La ribonucleoprotein 4B) This gene encodes a member of an evolutionarily conserved protein family implicated in RNA metabolism and translation. Members of this family are characterized by the presence of an La motif, which is often located adjacent to one or more RNA recognition motifs (RRM). Together, the two motifs constitute the functional region of the protein and enable its interaction with the RNA substrate. This protein family is divided into five sub-families: the genuine La proteins and four La-related protein (LARP) sub-families. The protein encoded by this gene belongs to LARP sub-family 4. It is a cytoplasmic protein that may play a stimulatory role in translation. [provided by RefSeq, Oct 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015155.3. 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
	LARP4B	NM_015155.3	MANE Select	c.*1948T>A		3_prime_UTR	Exon 18 of 18	NP_055970.1	Q92615
	LARP4B	NM_001351277.2		c.*1948T>A		3_prime_UTR	Exon 18 of 18	NP_001338206.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP4B	ENST00000316157.8	TSL:1 MANE Select	c.*1948T>A		3_prime_UTR	Exon 18 of 18	ENSP00000326128.3	Q92615
	LARP4B	ENST00000689323.1		c.*1948T>A		3_prime_UTR	Exon 16 of 16	ENSP00000510165.1	A0A8I5KVU2
	LARP4B	ENST00000860824.1		c.*1948T>A		3_prime_UTR	Exon 18 of 18	ENSP00000530883.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62261 AN: 151994 Hom.: 13277 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.401

GnomAD4 exome AF: 0.833 AC: 5 AN: 6 Hom.: 2 Cov.: 0 AF XY: 0.833 AC XY: 5 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.833 AC: 5 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.410 AC: 62343 AN: 152112 Hom.: 13305 Cov.: 33 AF XY: 0.413 AC XY: 30700 AN XY: 74332

African (AFR) AF: 0.311 AC: 12911 AN: 41506

American (AMR) AF: 0.367 AC: 5608 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1925 AN: 5176

South Asian (SAS) AF: 0.486 AC: 2342 AN: 4822

European-Finnish (FIN) AF: 0.537 AC: 5659 AN: 10536

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31179 AN: 67988

Other (OTH) AF: 0.407 AC: 859 AN: 2110

Alfa AF: 0.433 Hom.: 1818

Bravo AF: 0.389

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.47
PhyloP100		0.88
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: rs4229; hg19: chr10-856918;