11-61509603-C-T

Variant names:

• chr11-61509603-C-T
• rs930947709
• NM_001145077.2:c.605C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001145077.2(LRRC10B):​c.605C>T​(p.Pro202Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000584 in 1,369,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P202R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: LRRC10B NM_001145077.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10427183).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC10B	NM_001145077.2	c.605C>T	p.Pro202Leu	missense_variant	Exon 1 of 1	ENST00000378075.4	NP_001138549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC10B	ENST00000378075.4	c.605C>T	p.Pro202Leu	missense_variant	Exon 1 of 1	6	NM_001145077.2	ENSP00000367315.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000584 AC: 8 AN: 1369364 Hom.: 0 Cov.: 33 AF XY: 0.00000592 AC XY: 4 AN XY: 675952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000545

Gnomad4 NFE exome AF: 0.00000466

Gnomad4 OTH exome AF: 0.0000175

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.47	N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.038
Sift	Benign	0.14	T
Sift4G	Benign	0.61	T
Polyphen		0.052	B
Vest4		0.11
MutPred		0.36		Loss of disorder (P = 0.0909);
MVP		0.30
ClinPred		0.47	T
GERP RS		3.5
Varity_R		0.13
gMVP		0.24

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: rs930947709; hg19: chr11-61277075;