Variant 7-108030855-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_007356.3(LAMB4):c.4943C>T(p.Ala1648Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

LAMB4
NM_007356.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.249

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0046325624).

BP6

Variant 7-108030855-G-A is Benign according to our data. Variant chr7-108030855-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3290032.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMB4	NM_007356.3 linkuse as main transcript	c.4943C>T	p.Ala1648Val	missense_variant	32/34	ENST00000388781.8	NP_031382.2	A4D0S4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAMB4	ENST00000388781.8 linkuse as main transcript	c.4943C>T	p.Ala1648Val	missense_variant	32/34	1	NM_007356.3	ENSP00000373433.3	A4D0S4-1
LAMB4	ENST00000205386.8 linkuse as main transcript	c.4943C>T	p.Ala1648Val	missense_variant	32/34	1		ENSP00000205386.4	A4D0S4-1
LAMB4	ENST00000422975.1 linkuse as main transcript	c.2021C>T	p.Ala674Val	missense_variant	11/13	1		ENSP00000416562.1	A0A0C4DG90
LAMB4	ENST00000483484.5 linkuse as main transcript	n.215-1659C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000271

AC:

AN:

251338

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000123

AC:

180

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000631

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000246

Hom.:

Bravo

AF:

0.000657

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.9

DANN

Benign

0.73

DEOGEN2

Benign

0.099

T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.42

.;T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.0046

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-0.74

N;N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.60

N;N;N

REVEL

Benign

0.065

Sift

Benign

0.68

T;T;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.13

MVP

0.014

MPC

0.064

ClinPred

0.0089

GERP RS

-3.4

Varity_R

0.027

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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