chr20-62345644-T-C

Variant names:

• chr20-62345644-T-C
• rs6143035
• NM_005560.6:c.1477+174A>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.1477+174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 644,594 control chromosomes in the GnomAD database, including 17,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4847 hom., cov: 33)
  • Exomes 𝑓: 0.22 (12785 hom.)
• Consequence: LAMA5 NM_005560.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.899
• Publications: 11 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):

• nephrotic syndrome, IIa 26

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• LAMA5-related multisystemic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC124904946 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-62345644-T-C is Benign according to our data. Variant chr20-62345644-T-C is described in ClinVar as Benign. ClinVar VariationId is 1294795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA5	NM_005560.6	c.1477+174A>G		intron_variant	Intron 11 of 79	ENST00000252999.7	NP_005551.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA5	ENST00000252999.7	c.1477+174A>G		intron_variant	Intron 11 of 79	1	NM_005560.6	ENSP00000252999.3
LAMA5	ENST00000370677.4	n.1503-59A>G		intron_variant	Intron 11 of 11	2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37215 AN: 152058 Hom.: 4839 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.224 AC: 110186 AN: 492418 Hom.: 12785 Cov.: 5 AF XY: 0.224 AC XY: 58706 AN XY: 262374

African (AFR) AF: 0.322 AC: 4428 AN: 13758

American (AMR) AF: 0.138 AC: 3147 AN: 22886

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 3146 AN: 16020

East Asian (EAS) AF: 0.165 AC: 5162 AN: 31286

South Asian (SAS) AF: 0.206 AC: 10579 AN: 51248

European-Finnish (FIN) AF: 0.175 AC: 5513 AN: 31464

Middle Eastern (MID) AF: 0.227 AC: 853 AN: 3758

European-Non Finnish (NFE) AF: 0.242 AC: 71118 AN: 294074

Other (OTH) AF: 0.223 AC: 6240 AN: 27924

GnomAD4 genome AF: 0.245 AC: 37245 AN: 152176 Hom.: 4847 Cov.: 33 AF XY: 0.238 AC XY: 17685 AN XY: 74404

African (AFR) AF: 0.329 AC: 13659 AN: 41486

American (AMR) AF: 0.170 AC: 2595 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3470

East Asian (EAS) AF: 0.192 AC: 994 AN: 5176

South Asian (SAS) AF: 0.190 AC: 915 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1888 AN: 10610

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15902 AN: 68000

Other (OTH) AF: 0.222 AC: 469 AN: 2110

Alfa AF: 0.235 Hom.: 2806

Bravo AF: 0.249

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.75
DANN	Benign	0.56
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6143035; hg19: chr20-60920700; COSMIC: COSV107265310; COSMIC: COSV107265310;