20-62345988-T-C

Variant names:

• chr20-62345988-T-C
• rs4925386
• NM_005560.6:c.1417+93A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005560.6(LAMA5):​c.1417+93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,582,194 control chromosomes in the GnomAD database, including 354,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (27142 hom., cov: 32)
  • Exomes 𝑓: 0.67 (327617 hom.)
• Consequence: LAMA5 NM_005560.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.579
• Publications: 138 publications found

Genes affected

LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]

LAMA5 Gene-Disease associations (from GenCC):

• LAMA5-related multisystemic syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• nephrotic syndrome, IIa 26

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC124904946 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-62345988-T-C is Benign according to our data. Variant chr20-62345988-T-C is described in ClinVar as Benign. ClinVar VariationId is 1297291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005560.6. 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
	LAMA5	NM_005560.6	MANE Select	c.1417+93A>G		intron	N/A	NP_005551.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA5	ENST00000252999.7	TSL:1 MANE Select	c.1417+93A>G		intron	N/A	ENSP00000252999.3	O15230-1
	LAMA5	ENST00000370677.4	TSL:2	n.1442+93A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85738 AN: 151944 Hom.: 27139 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.672 AC: 961514 AN: 1430132 Hom.: 327617 Cov.: 27 AF XY: 0.672 AC XY: 476871 AN XY: 709932

African (AFR) AF: 0.229 AC: 7540 AN: 32934

American (AMR) AF: 0.695 AC: 30338 AN: 43640

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 17679 AN: 25100

East Asian (EAS) AF: 0.783 AC: 30704 AN: 39220

South Asian (SAS) AF: 0.603 AC: 50667 AN: 83964

European-Finnish (FIN) AF: 0.678 AC: 34786 AN: 51334

Middle Eastern (MID) AF: 0.641 AC: 3542 AN: 5528

European-Non Finnish (NFE) AF: 0.686 AC: 747343 AN: 1089398

Other (OTH) AF: 0.659 AC: 38915 AN: 59014

GnomAD4 genome AF: 0.564 AC: 85758 AN: 152062 Hom.: 27142 Cov.: 32 AF XY: 0.567 AC XY: 42137 AN XY: 74320

African (AFR) AF: 0.249 AC: 10314 AN: 41494

American (AMR) AF: 0.636 AC: 9732 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2499 AN: 3472

East Asian (EAS) AF: 0.752 AC: 3856 AN: 5130

South Asian (SAS) AF: 0.608 AC: 2927 AN: 4818

European-Finnish (FIN) AF: 0.675 AC: 7138 AN: 10574

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47064 AN: 67960

Other (OTH) AF: 0.617 AC: 1303 AN: 2112

Alfa AF: 0.650 Hom.: 135236

Bravo AF: 0.547

Asia WGS AF: 0.660 AC: 2295 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.57
PhyloP100		-0.58
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: rs4925386; hg19: chr20-60921044; COSMIC: COSV53370159; COSMIC: COSV53370159;