7-108107020-C-T

Variant names:

• chr7-108107020-C-T
• rs425623
• NM_007356.3:c.592-448G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007356.3(LAMB4):​c.592-448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,924 control chromosomes in the GnomAD database, including 10,984 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 0.37 (10984 hom., cov: 33)
• Consequence: LAMB4 NM_007356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB4	NM_007356.3	c.592-448G>A		intron_variant	Intron 6 of 33	ENST00000388781.8	NP_031382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMB4	ENST00000388781.8	c.592-448G>A		intron_variant	Intron 6 of 33	1	NM_007356.3	ENSP00000373433.3
LAMB4	ENST00000205386.8	c.592-448G>A		intron_variant	Intron 6 of 33	1		ENSP00000205386.4
LAMB4	ENST00000418464.1	c.592-448G>A		intron_variant	Intron 6 of 17	1		ENSP00000402353.2
LAMB4	ENST00000475469.1	n.676-448G>A		intron_variant	Intron 6 of 22	2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56206 AN: 151806 Hom.: 10978 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.370 AC: 56238 AN: 151924 Hom.: 10984 Cov.: 33 AF XY: 0.376 AC XY: 27893 AN XY: 74258

African (AFR) AF: 0.260 AC: 10760 AN: 41404

American (AMR) AF: 0.407 AC: 6211 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1109 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2020 AN: 5160

South Asian (SAS) AF: 0.378 AC: 1817 AN: 4812

European-Finnish (FIN) AF: 0.461 AC: 4869 AN: 10552

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28281 AN: 67944

Other (OTH) AF: 0.354 AC: 749 AN: 2116

Alfa AF: 0.388 Hom.: 1532

Bravo AF: 0.358

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.42
PhyloP100		-0.059
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: rs425623; hg19: chr7-107747465;