Genetic Variant LRRC74A:p.Val433Glu (chr14-76866065-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385106.1(LRRC74A):c.1298T>A(p.Val433Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,405,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LRRC74A
NM_001385106.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.322

Publications

0 publications found

Variant links:

Genes affected

LRRC74A (HGNC:23346): (leucine rich repeat containing 74A)

LRRC74A links:

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ACMG classification

Classification was made for transcript

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=0.12673017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC74A	NM_001385106.1 link	c.1298T>A	p.Val433Glu	missense_variant	Exon 12 of 14	ENST00000689127.1	NP_001372035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC74A	ENST00000689127.1 link	c.1298T>A	p.Val433Glu	missense_variant	Exon 12 of 14		NM_001385106.1	ENSP00000509938.1		A0A8I5KW16

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.11e-7

AC:

AN:

1405542

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699384

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32474

American (AMR)

AF:

0.00

AC:

AN:

41668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25664

East Asian (EAS)

AF:

0.00

AC:

AN:

39090

South Asian (SAS)

AF:

0.00

AC:

AN:

82558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

9.37e-7

AC:

AN:

1067334

Other (OTH)

AF:

0.00

AC:

AN:

58662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.026

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.35

M_CAP

Benign

0.0064

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

PhyloP100

0.32

PROVEAN

Benign

-0.21

REVEL

Benign

0.025

Sift

Benign

0.032

Sift4G

Uncertain

0.018

Polyphen

0.20

Vest4

0.26

MutPred

0.60

Gain of disorder (P = 0.005);

MVP

0.21

MPC

0.055

ClinPred

0.14

GERP RS

0.54

Varity_R

0.10

gMVP

0.69

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over