Variant 19-49114875-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022165.3(LIN7B):c.64G>C(p.Glu22Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000136 in 1,472,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

LIN7B
NM_022165.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

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]

LIN7B links:

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ACMG classification

Classification made for transcript

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=0.31440103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN7B	NM_022165.3 linkuse as main transcript	c.64G>C	p.Glu22Gln	missense_variant	2/6	ENST00000221459.7	NP_071448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN7B	ENST00000221459.7 linkuse as main transcript	c.64G>C	p.Glu22Gln	missense_variant	2/6	1	NM_022165.3	ENSP00000221459	P1	Q9HAP6-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.58e-7

AC:

AN:

1320030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

650928

show subpopulations

Gnomad4 AFR exome

AF:

0.0000371

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

The c.64G>C (p.E22Q) alteration is located in exon 2 (coding exon 2) of the LIN7B gene. This alteration results from a G to C substitution at nucleotide position 64, causing the glutamic acid (E) at amino acid position 22 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

.;T

Eigen

Benign

-0.059

Eigen_PC

Benign

0.024

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.056

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.16

Sift

Benign

0.040

D;T

Sift4G

Benign

0.098

T;T

Polyphen

0.057

.;B

Vest4

0.24

MutPred

0.64

Gain of MoRF binding (P = 0.0237);Gain of MoRF binding (P = 0.0237);

MVP

0.48

MPC

0.58

ClinPred

0.90

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over