Variant 7-108030844-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_007356.3(LAMB4):c.4954G>C(p.Ala1652Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,860 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: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LAMB4
NM_007356.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

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:

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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=0.3820377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMB4	NM_007356.3 linkuse as main transcript	c.4954G>C	p.Ala1652Pro	missense_variant	32/34	ENST00000388781.8	NP_031382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMB4	ENST00000388781.8 linkuse as main transcript	c.4954G>C	p.Ala1652Pro	missense_variant	32/34	1	NM_007356.3	ENSP00000373433	P1	A4D0S4-1
LAMB4	ENST00000205386.8 linkuse as main transcript	c.4954G>C	p.Ala1652Pro	missense_variant	32/34	1		ENSP00000205386	P1	A4D0S4-1
LAMB4	ENST00000422975.1 linkuse as main transcript	c.2032G>C	p.Ala678Pro	missense_variant	11/13	1		ENSP00000416562
LAMB4	ENST00000483484.5 linkuse as main transcript	n.215-1648G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

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:

0.00000180

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

Oct 06, 2021

The c.4954G>C (p.A1652P) alteration is located in exon 32 (coding exon 31) of the LAMB4 gene. This alteration results from a G to C substitution at nucleotide position 4954, causing the alanine (A) at amino acid position 1652 to be replaced by a proline (P). 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

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.54

.;T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Uncertain

0.11

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.012

D;D;T

Polyphen

1.0

D;D;.

Vest4

0.60

MutPred

0.37

Loss of MoRF binding (P = 0.1005);Loss of MoRF binding (P = 0.1005);.;

MVP

0.28

MPC

0.44

ClinPred

0.99

GERP RS

5.2

Varity_R

0.86

gMVP

0.67

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

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