chr19-49114903-C-A

Variant names:

• chr19-49114903-C-A
• rs751697792
• NM_022165.3:c.92C>A

Variant summary

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

The NM_022165.3(LIN7B):​c.92C>A​(p.Pro31Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000757 in 1,321,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P31L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: LIN7B NM_022165.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67
• Publications: 0 publications found

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]

ENSG00000297778 (HGNC:):

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=0.4194858).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022165.3. 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
	LIN7B	NM_022165.3	MANE Select	c.92C>A	p.Pro31Gln	missense	Exon 2 of 6	NP_071448.1	Q9HAP6-1
	LIN7B	NM_001308419.2		c.92C>A	p.Pro31Gln	missense	Exon 2 of 5	NP_001295348.1	Q9HAP6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN7B	ENST00000221459.7	TSL:1 MANE Select	c.92C>A	p.Pro31Gln	missense	Exon 2 of 6	ENSP00000221459.2	Q9HAP6-1
	LIN7B	ENST00000882750.1		c.92C>A	p.Pro31Gln	missense	Exon 2 of 5	ENSP00000552809.1
	LIN7B	ENST00000391864.7	TSL:3	c.92C>A	p.Pro31Gln	missense	Exon 2 of 5	ENSP00000375737.3	Q9HAP6-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1321240 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 651920

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000366 AC: 1 AN: 27306

American (AMR) AF: 0.00 AC: 0 AN: 28368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22784

East Asian (EAS) AF: 0.00 AC: 0 AN: 30220

South Asian (SAS) AF: 0.00 AC: 0 AN: 72802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4508

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1045540

Other (OTH) AF: 0.00 AC: 0 AN: 53990

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	0.18
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.7
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.17
Sift	Benign	0.053	T
Sift4G	Uncertain	0.040	D
Polyphen		0.54	P
Vest4		0.46
MutPred		0.52		Gain of sheet (P = 0.0073)
MVP		0.39
MPC		0.79
ClinPred		0.99	D
GERP RS		3.2
PromoterAI		-0.035	Neutral
Varity_R		0.45
gMVP		0.69
Mutation Taster		=54/46	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: rs751697792; hg19: chr19-49618160;