rs7160583

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-76866065-T-A
• chr14-76866065-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194287.3(LRRC74A):​c.1349T>A​(p.Val450Glu) 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_194287.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 0 publications found

Genes affected

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

ACMG classification

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).

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>A	p.Val433Glu	missense	Exon 12 of 14	NP_001372035.1
	LRRC74A	NM_194287.3		c.1349T>A	p.Val450Glu	missense	Exon 12 of 14	NP_919263.2
	LRRC74A	NM_001385107.1		c.1277T>A	p.Val426Glu	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>A	p.Val433Glu	missense	Exon 12 of 14	ENSP00000509938.1
	LRRC74A	ENST00000393774.7	TSL:1	c.1349T>A	p.Val450Glu	missense	Exon 12 of 14	ENSP00000377369.3
	LRRC74A	ENST00000691684.1		c.1166T>A	p.Val389Glu	missense	Exon 10 of 12	ENSP00000509131.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1405542 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 699384

African (AFR) AF: 0.00 AC: 0 AN: 32474

American (AMR) AF: 0.00 AC: 0 AN: 41668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25664

East Asian (EAS) AF: 0.00 AC: 0 AN: 39090

South Asian (SAS) AF: 0.00 AC: 0 AN: 82558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1067334

Other (OTH) AF: 0.00 AC: 0 AN: 58662

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.32
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.025
Sift	Benign	0.032	D
Sift4G	Uncertain	0.018	D
Polyphen		0.20	B
Vest4		0.26
MutPred		0.60		Gain of disorder (P = 0.005)
MVP		0.21
MPC		0.055
ClinPred		0.14	T
GERP RS		0.54
Varity_R		0.10
gMVP		0.69
Mutation Taster		=99/1	polymorphism

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;