rs7160583

chr14-76866065-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385106.1(LRRC74A):c.1298T>C(p.Val433Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,555,352 control chromosomes in the GnomAD database, including 81,092 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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: 𝑓 0.29 (6694 hom., cov: 32)
  • Exomes 𝑓: 0.32 (74398 hom.)
• Consequence: LRRC74A NM_001385106.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041403174).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC74A	NM_001385106.1	c.1298T>C	p.Val433Ala	missense_variant	12/14	ENST00000689127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC74A	ENST00000689127.1	c.1298T>C	p.Val433Ala	missense_variant	12/14		NM_001385106.1	P2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44083 AN: 151878 Hom.: 6689 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.0876

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.304

GnomAD3 exomes AF: 0.285 AC: 62933 AN: 220748 Hom.: 9334 AF XY: 0.286 AC XY: 33977 AN XY: 118888

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.276

Gnomad ASJ exome AF: 0.310

Gnomad EAS exome AF: 0.0916

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.334

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.320 AC: 448760 AN: 1403356 Hom.: 74398 Cov.: 32 AF XY: 0.317 AC XY: 221285 AN XY: 698344

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.0820

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.290 AC: 44101 AN: 151996 Hom.: 6694 Cov.: 32 AF XY: 0.286 AC XY: 21237 AN XY: 74288

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.0878

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.302

Alfa AF: 0.322 Hom.: 16983

Bravo AF: 0.284

TwinsUK AF: 0.344 AC: 1276

ALSPAC AF: 0.346 AC: 1334

ESP6500AA AF: 0.218 AC: 905

ESP6500EA AF: 0.339 AC: 2856

ExAC AF: 0.268 AC: 32267

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.63
Dann	Benign	0.22
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00095	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	P
PROVEAN	Benign	1.8	N
REVEL	Benign	0.030
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.011
MPC		0.035
ClinPred		0.00091	T
GERP RS		0.54
Varity_R		0.023
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs7160583; hg19: chr14-77332408; COSMIC: COSV53611484;