rs9690688

Variant names:

• chr7-108079717-C-A
• rs9690688
• NM_007356.3:c.1771G>T

Variant summary

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

The NM_007356.3(LAMB4):​c.1771G>T​(p.Val591Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 1,611,290 control chromosomes in the GnomAD database, including 10,308 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (3872 hom., cov: 32)
  • Exomes 𝑓: 0.075 (6436 hom.)
• Consequence: LAMB4 NM_007356.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 17 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 (MetaRNN=0.0025619268).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007356.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB4	NM_007356.3	MANE Select	c.1771G>T	p.Val591Phe	missense	Exon 15 of 34	NP_031382.2	A4D0S4-1
	LAMB4	NM_001318046.2		c.1771G>T	p.Val591Phe	missense	Exon 15 of 34	NP_001304975.1	A4D0S4-1
	LAMB4	NM_001318047.2		c.1771G>T	p.Val591Phe	missense	Exon 15 of 23	NP_001304976.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB4	ENST00000388781.8	TSL:1 MANE Select	c.1771G>T	p.Val591Phe	missense	Exon 15 of 34	ENSP00000373433.3	A4D0S4-1
	LAMB4	ENST00000205386.8	TSL:1	c.1771G>T	p.Val591Phe	missense	Exon 15 of 34	ENSP00000205386.4	A4D0S4-1
	LAMB4	ENST00000418464.1	TSL:1	c.1771G>T	p.Val591Phe	missense	Exon 15 of 18	ENSP00000402353.2	C9JMJ0

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24723 AN: 151964 Hom.: 3862 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.00886

Gnomad SAS AF: 0.0748

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.0886 AC: 21964 AN: 247896 AF XY: 0.0823

Gnomad AFR exome AF: 0.420

Gnomad AMR exome AF: 0.0900

Gnomad ASJ exome AF: 0.0796

Gnomad EAS exome AF: 0.00770

Gnomad FIN exome AF: 0.0621

Gnomad NFE exome AF: 0.0643

Gnomad OTH exome AF: 0.0776

GnomAD4 exome AF: 0.0746 AC: 108808 AN: 1459208 Hom.: 6436 Cov.: 31 AF XY: 0.0736 AC XY: 53385 AN XY: 725772

African (AFR) AF: 0.430 AC: 14356 AN: 33404

American (AMR) AF: 0.0906 AC: 4008 AN: 44220

Ashkenazi Jewish (ASJ) AF: 0.0786 AC: 2049 AN: 26064

East Asian (EAS) AF: 0.0141 AC: 558 AN: 39550

South Asian (SAS) AF: 0.0751 AC: 6416 AN: 85470

European-Finnish (FIN) AF: 0.0659 AC: 3517 AN: 53386

Middle Eastern (MID) AF: 0.0944 AC: 544 AN: 5760

European-Non Finnish (NFE) AF: 0.0647 AC: 71829 AN: 1111034

Other (OTH) AF: 0.0917 AC: 5531 AN: 60320

GnomAD4 genome AF: 0.163 AC: 24769 AN: 152082 Hom.: 3872 Cov.: 32 AF XY: 0.157 AC XY: 11681 AN XY: 74350

African (AFR) AF: 0.411 AC: 17028 AN: 41398

American (AMR) AF: 0.106 AC: 1622 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3466

East Asian (EAS) AF: 0.00907 AC: 47 AN: 5180

South Asian (SAS) AF: 0.0741 AC: 357 AN: 4820

European-Finnish (FIN) AF: 0.0677 AC: 718 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0639 AC: 4344 AN: 68020

Other (OTH) AF: 0.135 AC: 285 AN: 2110

Alfa AF: 0.0929 Hom.: 5815

Bravo AF: 0.179

TwinsUK AF: 0.0674 AC: 250

ALSPAC AF: 0.0654 AC: 252

ESP6500AA AF: 0.396 AC: 1746

ESP6500EA AF: 0.0673 AC: 579

ExAC AF: 0.0942 AC: 11434

Asia WGS AF: 0.0700 AC: 244 AN: 3478

EpiCase AF: 0.0642

EpiControl AF: 0.0645

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.26
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.062
Sift	Benign	0.045	D
Sift4G	Uncertain	0.019	D
Polyphen		0.93	P
Vest4		0.14
MPC		0.26
ClinPred		0.024	T
GERP RS		1.5
Varity_R		0.13
gMVP		0.65
Mutation Taster		=99/1	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: rs9690688; hg19: chr7-107720162; COSMIC: COSV52719229;