rs448559

chr7-108099040-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007356.3(LAMB4):c.1181-458T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,142 control chromosomes in the GnomAD database, including 9,623 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 0.35 (9623 hom., cov: 33)
• Consequence: LAMB4 NM_007356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMB4	NM_007356.3	c.1181-458T>C		intron_variant		ENST00000388781.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMB4	ENST00000388781.8	c.1181-458T>C		intron_variant		1	NM_007356.3	P1
LAMB4	ENST00000205386.8	c.1181-458T>C		intron_variant		1		P1
LAMB4	ENST00000418464.1	c.1181-458T>C		intron_variant		1
LAMB4	ENST00000475469.1	n.1265-458T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52738 AN: 152024 Hom.: 9621 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.334

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.347 AC: 52759 AN: 152142 Hom.: 9623 Cov.: 33 AF XY: 0.348 AC XY: 25877 AN XY: 74370

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.331

Alfa AF: 0.368 Hom.: 1458

Bravo AF: 0.338

Asia WGS AF: 0.246 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	14
Dann	Benign	0.75

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: rs448559; hg19: chr7-107739485;