14-76866065-T-C

Variant names:

• chr14-76866065-T-C
• rs7160583
• NM_001385106.1:c.1298T>C

Variant summary

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

The NM_194287.3(LRRC74A):​c.1349T>C​(p.Val450Ala) 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. 13/19 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_194287.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 24 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194287.3. 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
	LRRC74A	NM_001385106.1	MANE Select	c.1298T>C	p.Val433Ala	missense	Exon 12 of 14	NP_001372035.1
	LRRC74A	NM_194287.3		c.1349T>C	p.Val450Ala	missense	Exon 12 of 14	NP_919263.2
	LRRC74A	NM_001385107.1		c.1277T>C	p.Val426Ala	missense	Exon 12 of 14	NP_001372036.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC74A	ENST00000689127.1	MANE Select	c.1298T>C	p.Val433Ala	missense	Exon 12 of 14	ENSP00000509938.1
	LRRC74A	ENST00000393774.7	TSL:1	c.1349T>C	p.Val450Ala	missense	Exon 12 of 14	ENSP00000377369.3
	LRRC74A	ENST00000691684.1		c.1166T>C	p.Val389Ala	missense	Exon 10 of 12	ENSP00000509131.1

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

GnomAD2 exomes AF: 0.285 AC: 62933 AN: 220748 AF XY: 0.286

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 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

African (AFR) AF: 0.216 AC: 7005 AN: 32438

American (AMR) AF: 0.278 AC: 11589 AN: 41638

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 8202 AN: 25644

East Asian (EAS) AF: 0.0820 AC: 3204 AN: 39070

South Asian (SAS) AF: 0.215 AC: 17703 AN: 82512

European-Finnish (FIN) AF: 0.333 AC: 17445 AN: 52368

Middle Eastern (MID) AF: 0.286 AC: 1623 AN: 5680

European-Non Finnish (NFE) AF: 0.342 AC: 364035 AN: 1065410

Other (OTH) AF: 0.306 AC: 17954 AN: 58596

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

African (AFR) AF: 0.224 AC: 9297 AN: 41472

American (AMR) AF: 0.294 AC: 4480 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1156 AN: 3472

East Asian (EAS) AF: 0.0878 AC: 454 AN: 5172

South Asian (SAS) AF: 0.196 AC: 943 AN: 4816

European-Finnish (FIN) AF: 0.330 AC: 3481 AN: 10562

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.342 AC: 23254 AN: 67932

Other (OTH) AF: 0.302 AC: 636 AN: 2108

Alfa AF: 0.317 Hom.: 32315

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 v4.9

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
PhyloP100		0.32
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
Mutation Taster		=99/1	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: rs7160583; hg19: chr14-77332408; COSMIC: COSV53611484;