Variant 7-108030915-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007356.3(LAMB4):c.4883A>G(p.Glu1628Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,062 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

LAMB4
NM_007356.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.845

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:

LAMB4 (HGNC:):

LAMB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016726285).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMB4	NM_007356.3 linkuse as main transcript	c.4883A>G	p.Glu1628Gly	missense_variant	32/34	ENST00000388781.8	NP_031382.2	A4D0S4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMB4	ENST00000388781.8 linkuse as main transcript	c.4883A>G	p.Glu1628Gly	missense_variant	32/34	1	NM_007356.3	ENSP00000373433.3		A4D0S4-1

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000521

AC:

131

AN:

251326

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000898

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00108

AC:

1576

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

750

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00135

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.000598

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000918

Hom.:

Bravo

AF:

0.000608

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000469

AC:

EpiCase

AF:

0.000982

EpiControl

AF:

0.000652

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

Jun 18, 2021

The c.4883A>G (p.E1628G) alteration is located in exon 32 (coding exon 31) of the LAMB4 gene. This alteration results from a A to G substitution at nucleotide position 4883, causing the glutamic acid (E) at amino acid position 1628 to be replaced by a glycine (G). 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

0.086

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.41

T;T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.50

.;T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.0

M;M;.

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Benign

0.017

Sift

Benign

0.076

T;T;D

Sift4G

Benign

0.26

T;T;D

Polyphen

0.73

P;P;.

Vest4

0.18

MVP

0.15

MPC

0.22

ClinPred

0.016

GERP RS

1.2

Varity_R

0.14

gMVP

0.19

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