NM_001080478.3:c.217G>A

Variant names:

• chr5-191755-G-A
• rs749692583
• NM_001080478.3:c.217G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080478.3(LRRC14B):​c.217G>A​(p.Asp73Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: LRRC14B NM_001080478.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.30
• Publications: 0 publications found

Genes affected

LRRC14B (HGNC:37268): (leucine rich repeat containing 14B) The protein encoded by this gene is a leucine-rich repeat containing protein that is a member of the PRAME family. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39170444).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080478.3. 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
	LRRC14B	NM_001080478.3	MANE Select	c.217G>A	p.Asp73Asn	missense	Exon 1 of 2	NP_001073947.1	A6NHZ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC14B	ENST00000328278.4	TSL:1 MANE Select	c.217G>A	p.Asp73Asn	missense	Exon 1 of 2	ENSP00000327675.3	A6NHZ5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000672 AC: 1 AN: 148914 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400358 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 691600

African (AFR) AF: 0.00 AC: 0 AN: 31932

American (AMR) AF: 0.00 AC: 0 AN: 36524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 36234

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082566

Other (OTH) AF: 0.00 AC: 0 AN: 58154

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		9.3
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.24
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.25		Gain of loop (P = 0.0851)
MVP		0.32
MPC		0.75
ClinPred		0.77	D
GERP RS		5.2
PromoterAI		0.041	Neutral
Varity_R		0.12
gMVP		0.42
Mutation Taster		=80/20	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: rs749692583; hg19: chr5-191870; COSMIC: COSV52045148; COSMIC: COSV52045148;