chr18-6985271-C-T

Position:

• chr18-6985271-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005559.4(LAMA1):​c.5626G>A​(p.Ala1876Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,613,800 control chromosomes in the GnomAD database, including 45,019 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (2926 hom., cov: 33)
  • Exomes 𝑓: 0.23 (42093 hom.)
• Consequence: LAMA1 NM_005559.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0480

Genes affected

LAMA1 (HGNC:6481): (laminin subunit alpha 1) This gene encodes one of the alpha 1 subunits of laminin. The laminins are a family of extracellular matrix glycoproteins that have a heterotrimeric structure consisting of an alpha, beta and gamma chain. These proteins make up a major component of the basement membrane and have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Mutations in this gene may be associated with Poretti-Boltshauser syndrome. [provided by RefSeq, Sep 2014]

LAMA1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038636029).
• BP6: Variant 18-6985271-C-T is Benign according to our data. Variant chr18-6985271-C-T is described in ClinVar as [Benign]. Clinvar id is 1168732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-6985271-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA1	NM_005559.4	c.5626G>A	p.Ala1876Thr	missense_variant	39/63	ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4	c.5626G>A	p.Ala1876Thr	missense_variant	39/63	1	NM_005559.4	ENSP00000374309.3
LAMA1	ENST00000579014.5	n.6641G>A		non_coding_transcript_exon_variant	38/62	2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26752 AN: 152080 Hom.: 2928 Cov.: 33

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.199

GnomAD3 exomes AF: 0.195 AC: 48968 AN: 251422 Hom.: 5419 AF XY: 0.200 AC XY: 27119 AN XY: 135888

Gnomad AFR exome AF: 0.0415

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.264

Gnomad EAS exome AF: 0.187

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.205

Gnomad NFE exome AF: 0.248

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.234 AC: 341884 AN: 1461602 Hom.: 42093 Cov.: 36 AF XY: 0.232 AC XY: 168977 AN XY: 727130

Gnomad4 AFR exome AF: 0.0391

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.176 AC: 26742 AN: 152198 Hom.: 2926 Cov.: 33 AF XY: 0.172 AC XY: 12763 AN XY: 74388

Gnomad4 AFR AF: 0.0458

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.198

Alfa AF: 0.234 Hom.: 10344

Bravo AF: 0.168

TwinsUK AF: 0.265 AC: 983

ALSPAC AF: 0.251 AC: 967

ESP6500AA AF: 0.0511 AC: 225

ESP6500EA AF: 0.256 AC: 2201

ExAC AF: 0.194 AC: 23568

Asia WGS AF: 0.167 AC: 581 AN: 3478

EpiCase AF: 0.258

EpiControl AF: 0.261

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	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.92
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.065
Sift	Benign	0.094	T
Sift4G	Benign	0.12	T
Polyphen		0.15	B
Vest4		0.016
MPC		0.11
ClinPred		0.0030	T
GERP RS		-0.59
Varity_R		0.037
gMVP		0.053

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: rs11664063; hg19: chr18-6985270; COSMIC: COSV67533858;