7-108024059-AT-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

The NM_007356.3(LAMB4):c.5265del(p.Lys1755AsnfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00973 in 1,607,420 control chromosomes in the GnomAD database, including 97 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (5 hom., cov: 33)
  • Exomes 𝑓: 0.010 (92 hom.)
• Consequence: LAMB4 NM_007356.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.633

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 Likely_benign. Variant got -2 ACMG points.

• PM4: Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 1760 codons.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMB4	NM_007356.3	c.5265del	p.Lys1755AsnfsTer11	frameshift_variant	34/34	ENST00000388781.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMB4	ENST00000388781.8	c.5265del	p.Lys1755AsnfsTer11	frameshift_variant	34/34	1	NM_007356.3	P1
LAMB4	ENST00000205386.8	c.5265del	p.Lys1755AsnfsTer11	frameshift_variant	34/34	1		P1
LAMB4	ENST00000483484.5	n.487del		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.00638 AC: 970 AN: 151992 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00303

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.00672

GnomAD3 exomes AF: 0.00741 AC: 1756 AN: 236956 Hom.: 18 AF XY: 0.00731 AC XY: 937 AN XY: 128148

Gnomad AFR exome AF: 0.00218

Gnomad AMR exome AF: 0.00334

Gnomad ASJ exome AF: 0.00429

Gnomad EAS exome AF: 0.000116

Gnomad SAS exome AF: 0.00316

Gnomad FIN exome AF: 0.00484

Gnomad NFE exome AF: 0.0123

Gnomad OTH exome AF: 0.00821

GnomAD4 exome AF: 0.0101 AC: 14675 AN: 1455310 Hom.: 92 Cov.: 29 AF XY: 0.00993 AC XY: 7188 AN XY: 723786

Gnomad4 AFR exome AF: 0.00151

Gnomad4 AMR exome AF: 0.00328

Gnomad4 ASJ exome AF: 0.00377

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00279

Gnomad4 FIN exome AF: 0.00559

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.00775

GnomAD4 genome AF: 0.00638 AC: 970 AN: 152110 Hom.: 5 Cov.: 33 AF XY: 0.00604 AC XY: 449 AN XY: 74374

Gnomad4 AFR AF: 0.00222

Gnomad4 AMR AF: 0.00367

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00303

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.00665

Alfa AF: 0.00574 Hom.: 2

Bravo AF: 0.00604

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs568834649; hg19: chr7-107664504;