rs448559

Variant names:

• chr7-108099040-A-G
• rs448559
• NM_007356.3:c.1181-458T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LAMB4	NM_007356.3	c.1181-458T>C		intron_variant	Intron 10 of 33	ENST00000388781.8	NP_031382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMB4	ENST00000388781.8	c.1181-458T>C		intron_variant	Intron 10 of 33	1	NM_007356.3	ENSP00000373433.3
LAMB4	ENST00000205386.8	c.1181-458T>C		intron_variant	Intron 10 of 33	1		ENSP00000205386.4
LAMB4	ENST00000418464.1	c.1181-458T>C		intron_variant	Intron 10 of 17	1		ENSP00000402353.2
LAMB4	ENST00000475469.1	n.1265-458T>C		intron_variant	Intron 10 of 22	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

African (AFR) AF: 0.267 AC: 11087 AN: 41520

American (AMR) AF: 0.376 AC: 5753 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1064 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1212 AN: 5172

South Asian (SAS) AF: 0.308 AC: 1483 AN: 4816

European-Finnish (FIN) AF: 0.382 AC: 4035 AN: 10566

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 27014 AN: 67982

Other (OTH) AF: 0.331 AC: 699 AN: 2114

Alfa AF: 0.364 Hom.: 1489

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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs448559; hg19: chr7-107739485;