19-49114439-G-T

Variant names:

• chr19-49114439-G-T
• rs1222092345
• NM_022165.3:c.35G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022165.3(LIN7B):​c.35G>T​(p.Arg12Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,056,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: LIN7B NM_022165.3 missense, splice_region
• Scores: Splicing: ADA: 0.3966
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03

Genes affected

LIN7B (HGNC:17788): (lin-7 homolog B, crumbs cell polarity complex component) Enables protein domain specific binding activity. Predicted to be involved in maintenance of epithelial cell apical/basal polarity; neurotransmitter secretion; and protein localization to basolateral plasma membrane. Predicted to be located in plasma membrane. Predicted to be part of MPP7-DLG1-LIN7 complex. Predicted to be active in basolateral plasma membrane; cell-cell junction; and synapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3153041).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN7B	NM_022165.3	c.35G>T	p.Arg12Leu	missense_variant, splice_region_variant	Exon 1 of 6	ENST00000221459.7	NP_071448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN7B	ENST00000221459.7	c.35G>T	p.Arg12Leu	missense_variant, splice_region_variant	Exon 1 of 6	1	NM_022165.3	ENSP00000221459.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000284 AC: 3 AN: 1056130 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 498388

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: 0.00

Gnomad4 NFE exome AF: 0.00000332

Gnomad4 OTH exome AF: 0.00

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	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	.;T
Eigen	Benign	-0.046
Eigen_PC	Benign	0.0072
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.0010	.;B
Vest4		0.51
MutPred		0.35		Loss of MoRF binding (P = 0.0773);Loss of MoRF binding (P = 0.0773);
MVP		0.65
MPC		0.65
ClinPred		0.99	D
GERP RS		2.5
Varity_R		0.57
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.40
dbscSNV1_RF	Benign	0.58
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: rs1222092345; hg19: chr19-49617696;