Variant 7-108029147-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007356.3(LAMB4):c.5042G>A(p.Ser1681Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,240 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LAMB4
NM_007356.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060790807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMB4	NM_007356.3 linkuse as main transcript	c.5042G>A	p.Ser1681Asn	missense_variant	33/34	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.5042G>A	p.Ser1681Asn	missense_variant	33/34	1	NM_007356.3	ENSP00000373433.3	A4D0S4-1
LAMB4	ENST00000205386.8 linkuse as main transcript	c.5042G>A	p.Ser1681Asn	missense_variant	33/34	1		ENSP00000205386.4	A4D0S4-1
LAMB4	ENST00000422975.1 linkuse as main transcript	c.2120G>A	p.Ser707Asn	missense_variant	12/13	1		ENSP00000416562.1	A0A0C4DG90
LAMB4	ENST00000483484.5 linkuse as main transcript	n.264G>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461240

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726890

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 13, 2024

The c.5042G>A (p.S1681N) alteration is located in exon 33 (coding exon 32) of the LAMB4 gene. This alteration results from a G to A substitution at nucleotide position 5042, causing the serine (S) at amino acid position 1681 to be replaced by an asparagine (N). 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

0.083

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.6

DANN

Benign

0.59

DEOGEN2

Benign

0.077

T;T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.41

.;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.061

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

L;L;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.25

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.12

MutPred

0.23

Loss of glycosylation at S1681 (P = 0.0168);Loss of glycosylation at S1681 (P = 0.0168);.;

MVP

0.18

MPC

0.061

ClinPred

0.13

GERP RS

3.5

Varity_R

0.039

gMVP

0.033

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over