7-108043829-C-A

Position:

• chr7-108043829-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The ENST00000388781.8(LAMB4):​c.4394G>T​(p.Gly1465Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,607,940 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (42 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (34 hom.)
• Consequence: LAMB4 ENST00000388781.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.704

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]

LAMB4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 7-108043829-C-A is Benign according to our data. Variant chr7-108043829-C-A is described in ClinVar as [Benign]. Clinvar id is 768193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1837/152020) while in subpopulation AFR AF= 0.0416 (1728/41490). AF 95% confidence interval is 0.04. There are 42 homozygotes in gnomad4. There are 883 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMB4	NM_007356.3	c.4394G>T	p.Gly1465Val	missense_variant	29/34	ENST00000388781.8	NP_031382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMB4	ENST00000388781.8	c.4394G>T	p.Gly1465Val	missense_variant	29/34	1	NM_007356.3	ENSP00000373433.3
LAMB4	ENST00000205386.8	c.4394G>T	p.Gly1465Val	missense_variant	29/34	1		ENSP00000205386.4
LAMB4	ENST00000422975.1	c.1472G>T	p.Gly491Val	missense_variant	8/13	1		ENSP00000416562.1
LAMB4	ENST00000475572.1	n.95G>T		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1839 AN: 151902 Hom.: 43 Cov.: 31

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00335

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00911

GnomAD3 exomes AF: 0.00349 AC: 862 AN: 246994 Hom.: 17 AF XY: 0.00250 AC XY: 334 AN XY: 133630

Gnomad AFR exome AF: 0.0436

Gnomad AMR exome AF: 0.00233

Gnomad ASJ exome AF: 0.00429

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000276

Gnomad OTH exome AF: 0.00251

GnomAD4 exome AF: 0.00140 AC: 2040 AN: 1455920 Hom.: 34 Cov.: 29 AF XY: 0.00121 AC XY: 878 AN XY: 724318

Gnomad4 AFR exome AF: 0.0416

Gnomad4 AMR exome AF: 0.00289

Gnomad4 ASJ exome AF: 0.00473

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000469

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000163

Gnomad4 OTH exome AF: 0.00349

GnomAD4 genome AF: 0.0121 AC: 1837 AN: 152020 Hom.: 42 Cov.: 31 AF XY: 0.0119 AC XY: 883 AN XY: 74306

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.00334

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00901

Alfa AF: 0.00235 Hom.: 10

Bravo AF: 0.0138

ESP6500AA AF: 0.0384 AC: 169

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.00408 AC: 495

Asia WGS AF: 0.00260 AC: 10 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.39
DEOGEN2	Benign	0.18	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.44	.;T;T
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N;N;D
REVEL	Benign	0.015
Sift	Uncertain	0.015	D;D;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.31	B;B;.
Vest4		0.27
MVP		0.014
MPC		0.085
ClinPred		0.0071	T
GERP RS		-2.4
Varity_R		0.073
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.48		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73424723; hg19: chr7-107684274;