Variant 7-108043779-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007356.3(LAMB4):c.4444A>C(p.Ile1482Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,592,948 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 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

LAMB4
NM_007356.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

LAMB4 (HGNC:6491): (laminin subunit beta 4) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in several processes, including basement membrane assembly; cell migration; and substrate adhesion-dependent cell spreading. Predicted to be located in basement membrane; extracellular region; and membrane. Predicted to be part of laminin complex. [provided by Alliance of Genome Resources, Apr 2022]

LAMB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08220148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMB4	NM_007356.3 linkuse as main transcript	c.4444A>C	p.Ile1482Leu	missense_variant	29/34	ENST00000388781.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMB4	ENST00000388781.8 linkuse as main transcript	c.4444A>C	p.Ile1482Leu	missense_variant	29/34	1	NM_007356.3	P1	A4D0S4-1
LAMB4	ENST00000205386.8 linkuse as main transcript	c.4444A>C	p.Ile1482Leu	missense_variant	29/34	1		P1	A4D0S4-1
LAMB4	ENST00000422975.1 linkuse as main transcript	c.1522A>C	p.Ile508Leu	missense_variant	8/13	1
LAMB4	ENST00000475572.1 linkuse as main transcript	n.145A>C		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000951

AC:

AN:

241842

Hom.:

AF XY:

0.000130

AC XY:

AN XY:

130660

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000391

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000958

AC:

138

AN:

1440714

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

717092

show subpopulations

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:

0.000312

Gnomad4 FIN exome

AF:

0.0000378

Gnomad4 NFE exome

AF:

0.0000937

Gnomad4 OTH exome

AF:

0.0000838

GnomAD4 genome

AF:

0.000112

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000133

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000132

AC:

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

Aug 15, 2023

The c.4444A>C (p.I1482L) alteration is located in exon 29 (coding exon 28) of the LAMB4 gene. This alteration results from a A to C substitution at nucleotide position 4444, causing the isoleucine (I) at amino acid position 1482 to be replaced by a leucine (L). 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

0.093

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

T;T;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.011

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.072

T;T;D

Sift4G

Benign

0.091

T;T;T

Polyphen

0.99

D;D;.

Vest4

0.56

MVP

0.055

MPC

0.070

ClinPred

0.29

GERP RS

4.9

Varity_R

0.16

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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