rs17154865

Positions:

• chr7-108055844-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LAMB4	NM_007356.3	c.3543G>A	p.Gln1181Gln	synonymous_variant	25/34	ENST00000388781.8	NP_031382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMB4	ENST00000388781.8	c.3543G>A	p.Gln1181Gln	synonymous_variant	25/34	1	NM_007356.3	ENSP00000373433.3
LAMB4	ENST00000205386.8	c.3543G>A	p.Gln1181Gln	synonymous_variant	25/34	1		ENSP00000205386.4
LAMB4	ENST00000422975.1	c.621G>A	p.Gln207Gln	synonymous_variant	4/13	1		ENSP00000416562.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27080 AN: 152050 Hom.: 7401 Cov.: 32

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

GnomAD3 exomes AF: 0.0558 AC: 14029 AN: 251402 Hom.: 3035 AF XY: 0.0446 AC XY: 6055 AN XY: 135864

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 SAS exome AF: 0.0175

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.: 32 AF XY: 0.0258 AC XY: 18779 AN XY: 727244

Gnomad4 AFR exome AF: 0.610

Gnomad4 AMR exome AF: 0.0486

Gnomad4 ASJ exome AF: 0.0332

Gnomad4 EAS exome AF: 0.00295

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.00339

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.0542

GnomAD4 genome AF: 0.178 AC: 27133 AN: 152168 Hom.: 7414 Cov.: 32 AF XY: 0.172 AC XY: 12832 AN XY: 74398

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.0849

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0216

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.151

Alfa AF: 0.0837 Hom.: 2130

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
DANN	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs17154865; hg19: chr7-107696289; COSMIC: COSV52719218;