NM_022165.3:c.35G>A

Variant names:

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

Variant summary

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

The NM_022165.3(LIN7B):​c.35G>A​(p.Arg12Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 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: 0.0000066 (0 hom.)
• Consequence: LIN7B NM_022165.3 missense, splice_region
• Scores: Splicing: ADA: 0.6477
• 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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2464546).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN7B	NM_022165.3	c.35G>A	p.Arg12Gln	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>A	p.Arg12Gln	missense_variant, splice_region_variant	Exon 1 of 6	1	NM_022165.3	ENSP00000221459.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000663 AC: 7 AN: 1056130 Hom.: 0 Cov.: 29 AF XY: 0.00000803 AC XY: 4 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: 0.000248

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	.;T
Eigen	Benign	-0.030
Eigen_PC	Benign	0.019
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.15
Sift	Benign	0.081	T;T
Sift4G	Uncertain	0.015	D;D
Polyphen		0.041	.;B
Vest4		0.30
MutPred		0.25		Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);
MVP		0.57
MPC		0.60
ClinPred		0.95	D
GERP RS		2.5
Varity_R		0.32
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.65
dbscSNV1_RF	Benign	0.69
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;