rs7227276

Variant names:

• chr18-7028455-G-A
• rs7227276
• NM_005559.4:c.2275-2349C>T

Variant summary

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

The NM_005559.4(LAMA1):​c.2275-2349C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,094 control chromosomes in the GnomAD database, including 4,274 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 0.23 (4274 hom., cov: 33)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA1	NM_005559.4	c.2275-2349C>T		intron_variant	Intron 16 of 62	ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4	c.2275-2349C>T		intron_variant	Intron 16 of 62	1	NM_005559.4	ENSP00000374309.3
LAMA1	ENST00000579014.5	n.3290-2349C>T		intron_variant	Intron 15 of 61	2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34491 AN: 151976 Hom.: 4273 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00982

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.227 AC: 34509 AN: 152094 Hom.: 4274 Cov.: 33 AF XY: 0.225 AC XY: 16739 AN XY: 74350

African (AFR) AF: 0.305 AC: 12668 AN: 41480

American (AMR) AF: 0.149 AC: 2280 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3470

East Asian (EAS) AF: 0.00985 AC: 51 AN: 5180

South Asian (SAS) AF: 0.192 AC: 928 AN: 4824

European-Finnish (FIN) AF: 0.261 AC: 2755 AN: 10554

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14577 AN: 67990

Other (OTH) AF: 0.189 AC: 399 AN: 2110

Alfa AF: 0.212 Hom.: 14450

Bravo AF: 0.220

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.28
PhyloP100		0.11
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: rs7227276; hg19: chr18-7028454;