chr11-61509433-C-A

Variant names:

• chr11-61509433-C-A
• NM_001145077.2:c.435C>A

Variant summary

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

The NM_001145077.2(LRRC10B):​c.435C>A​(p.Asp145Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC10B NM_001145077.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17
• Publications: 0 publications found

Genes affected

LRRC10B (HGNC:37215): (leucine rich repeat containing 10B)

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=0.21245822).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145077.2. 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
	LRRC10B	NM_001145077.2	MANE Select	c.435C>A	p.Asp145Glu	missense	Exon 1 of 1	NP_001138549.1	A6NIK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC10B	ENST00000378075.4	TSL:6 MANE Select	c.435C>A	p.Asp145Glu	missense	Exon 1 of 1	ENSP00000367315.2	A6NIK2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1329300 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 654118

African (AFR) AF: 0.00 AC: 0 AN: 26298

American (AMR) AF: 0.00 AC: 0 AN: 25340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22420

East Asian (EAS) AF: 0.00 AC: 0 AN: 31622

South Asian (SAS) AF: 0.00 AC: 0 AN: 71470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4954

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1058994

Other (OTH) AF: 0.00 AC: 0 AN: 55208

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	Pathogenic	0.94
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.18
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.2
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.098
Sift	Benign	0.063	T
Sift4G	Benign	0.16	T
Polyphen		0.11	B
Vest4		0.35
MutPred		0.33		Gain of disorder (P = 0.0699)
MVP		0.048
ClinPred		0.87	D
GERP RS		3.2
Varity_R		0.35
gMVP		0.31
Mutation Taster		=71/29	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

hg19: chr11-61276905;