chr19-49114424-C-G

Variant names:

• chr19-49114424-C-G
• rs1250424914
• NM_022165.3:c.20C>G

Variant summary

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

The NM_022165.3(LIN7B):​c.20C>G​(p.Pro7Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000948 in 1,054,404 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. P7L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: LIN7B NM_022165.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39
• 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=0.32472664).

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.20C>G	p.Pro7Arg	missense	Exon 1 of 6	NP_071448.1	Q9HAP6-1
	LIN7B	NM_001308419.2		c.20C>G	p.Pro7Arg	missense	Exon 1 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.20C>G	p.Pro7Arg	missense	Exon 1 of 6	ENSP00000221459.2	Q9HAP6-1
	LIN7B	ENST00000882750.1		c.20C>G	p.Pro7Arg	missense	Exon 1 of 5	ENSP00000552809.1
	LIN7B	ENST00000391864.7	TSL:3	c.20C>G	p.Pro7Arg	missense	Exon 1 of 5	ENSP00000375737.3	Q9HAP6-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.48e-7 AC: 1 AN: 1054404 Hom.: 0 Cov.: 29 AF XY: 0.00000201 AC XY: 1 AN XY: 497594

African (AFR) AF: 0.00 AC: 0 AN: 21912

American (AMR) AF: 0.00 AC: 0 AN: 7500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13018

East Asian (EAS) AF: 0.00 AC: 0 AN: 24026

South Asian (SAS) AF: 0.00 AC: 0 AN: 19314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2766

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 903600

Other (OTH) AF: 0.00 AC: 0 AN: 41646

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.4
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.41	B
Vest4		0.38
MutPred		0.45		Gain of MoRF binding (P = 0.0105)
MVP		0.65
MPC		0.81
ClinPred		0.99	D
GERP RS		2.7
PromoterAI		0.0077	Neutral
Varity_R		0.68
gMVP		0.48
Mutation Taster		=49/51	disease causing

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: rs1250424914; hg19: chr19-49617681;