Variant chr18-6943172-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005559.4(LAMA1):c.9067+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,612,030 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

LAMA1
NM_005559.4 splice_region, intron

Scores

Splicing: ADA: 0.00003647

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.273

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 18-6943172-G-A is Benign according to our data. Variant chr18-6943172-G-A is described in ClinVar as [Benign]. Clinvar id is 733828.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-6943172-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA1	NM_005559.4 linkuse as main transcript	c.9067+8C>T		splice_region_variant, intron_variant		ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
LAMA1	ENST00000389658.4 linkuse as main transcript	c.9067+8C>T	splice_region_variant, intron_variant	1	NM_005559.4	ENSP00000374309	P1
LAMA1	ENST00000488064.5 linkuse as main transcript	n.2474+8C>T	splice_region_variant, intron_variant, non_coding_transcript_variant	2
LAMA1	ENST00000492048.5 linkuse as main transcript	n.1955+8C>T	splice_region_variant, intron_variant, non_coding_transcript_variant	2
LAMA1	ENST00000579014.5 linkuse as main transcript	n.10082+8C>T	splice_region_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000171

AC:

AN:

251098

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000297

AC:

434

AN:

1459730

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

218

AN XY:

726374

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000320

Gnomad4 OTH exome

AF:

0.000581

GnomAD4 genome

AF:

0.000151

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000262

Hom.:

Bravo

AF:

0.000185

EpiCase

AF:

0.000872

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.070

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over