dbSNP rs17154865: LAMB4:p.Gln1181Gln (chr7-108055844-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007356.3(LAMB4):c.3543G>A(p.Gln1181Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,614,042 control chromosomes in the GnomAD database, including 14,308 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 7414 hom., cov: 32)

Exomes 𝑓: 0.028 ( 6894 hom. )

Consequence

LAMB4
NM_007356.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP7

Synonymous conserved (PhyloP=-1.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB4	NM_007356.3 link	c.3543G>A	p.Gln1181Gln	synonymous_variant	Exon 25 of 34	ENST00000388781.8	NP_031382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
LAMB4	ENST00000388781.8 link	c.3543G>A	p.Gln1181Gln	synonymous_variant	Exon 25 of 34	1	NM_007356.3	ENSP00000373433.3
LAMB4	ENST00000205386.8 link	c.3543G>A	p.Gln1181Gln	synonymous_variant	Exon 25 of 34	1		ENSP00000205386.4
LAMB4	ENST00000422975.1 link	c.621G>A	p.Gln207Gln	synonymous_variant	Exon 4 of 13	1		ENSP00000416562.1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27080

AN:

152050

Hom.:

7401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.588

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0851

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.0220

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.153

GnomAD2 exomes

AF:

0.0558

AC:

14029

AN:

251402

AF XY:

0.0446

show subpopulations

Gnomad AFR exome

AF:

0.599

Gnomad AMR exome

AF:

0.0442

Gnomad ASJ exome

AF:

0.0341

Gnomad EAS exome

AF:

0.00353

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.0440

GnomAD4 exome

AF:

0.0278

AC:

40629

AN:

1461874

Hom.:

6894

Cov.:

AF XY:

0.0258

AC XY:

18779

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.610

AC:

20426

AN:

33476

American (AMR)

AF:

0.0486

AC:

2175

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0332

AC:

868

AN:

26136

East Asian (EAS)

AF:

0.00295

AC:

117

AN:

39700

South Asian (SAS)

AF:

0.0181

AC:

1563

AN:

86258

European-Finnish (FIN)

AF:

0.00339

AC:

181

AN:

53420

Middle Eastern (MID)

AF:

0.0775

AC:

447

AN:

5768

European-Non Finnish (NFE)

AF:

0.0104

AC:

11578

AN:

1111998

Other (OTH)

AF:

0.0542

AC:

3274

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1590

3180

4771

6361

7951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

716

1432

2148

2864

3580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.178

AC:

27133

AN:

152168

Hom.:

7414

Cov.:

AF XY:

0.172

AC XY:

12832

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.588

AC:

24368

AN:

41464

American (AMR)

AF:

0.0849

AC:

1298

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0340

AC:

118

AN:

3466

East Asian (EAS)

AF:

0.00367

AC:

AN:

5182

South Asian (SAS)

AF:

0.0216

AC:

104

AN:

4818

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0118

AC:

805

AN:

68014

Other (OTH)

AF:

0.151

AC:

319

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

608

1216

1825

2433

3041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0900

Hom.:

2456

Bravo

AF:

0.203

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

EpiCase

AF:

0.0176

EpiControl

AF:

0.0184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.16

(source)

DANN

Benign

0.79

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over