8-144520390-C-T

Position:

• chr8-144520390-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014665.4(LRRC14):​c.482C>T​(p.Ala161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC14 NM_014665.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.148

Genes affected

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058975875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC14	NM_014665.4	c.482C>T	p.Ala161Val	missense_variant	3/4	ENST00000292524.6	NP_055480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC14	ENST00000292524.6	c.482C>T	p.Ala161Val	missense_variant	3/4	1	NM_014665.4	ENSP00000292524	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455770 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724024

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 04, 2024

The c.482C>T (p.A161V) alteration is located in exon 3 (coding exon 2) of the LRRC14 gene. This alteration results from a C to T substitution at nucleotide position 482, causing the alanine (A) at amino acid position 161 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.5
DANN	Benign	0.78
DEOGEN2	Benign	0.032	.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.62	T;.;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.64	.;N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.87	N;N;N
REVEL	Benign	0.0080
Sift	Benign	0.53	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.19, 0.19
MutPred		0.24		Loss of disorder (P = 0.0821);Loss of disorder (P = 0.0821);Loss of disorder (P = 0.0821);
MVP		0.25
MPC		0.44
ClinPred		0.040	T
GERP RS		-3.0
Varity_R		0.030
gMVP		0.17

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145745774;