chr11-111541559-C-T

Position:

• chr11-111541559-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001258390.2(LAYN):​c.86-3C>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 0.00628 in 1,536,190 control chromosomes in the GnomAD database, including 43 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 0.0046 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (41 hom.)
• Consequence: LAYN NM_001258390.2 splice_region, intron
• Scores: Splicing: ADA: 0.001151
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.63

Genes affected

LAYN (HGNC:29471): (layilin) Enables hyaluronic acid binding activity. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 11-111541559-C-T is Benign according to our data. Variant chr11-111541559-C-T is described in ClinVar as [Benign]. Clinvar id is 1599865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAYN	NM_178834.5	c.85+631C>T		intron_variant		ENST00000375614.7	NP_849156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAYN	ENST00000375614.7	c.85+631C>T		intron_variant		1	NM_178834.5	ENSP00000364764.2

Frequencies

GnomAD3 genomes AF: 0.00457 AC: 695 AN: 152200 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00775

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00417 AC: 578 AN: 138534 Hom.: 2 AF XY: 0.00405 AC XY: 304 AN XY: 75004

Gnomad AFR exome AF: 0.000447

Gnomad AMR exome AF: 0.00265

Gnomad ASJ exome AF: 0.00372

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00200

Gnomad FIN exome AF: 0.00395

Gnomad NFE exome AF: 0.00707

Gnomad OTH exome AF: 0.00467

GnomAD4 exome AF: 0.00647 AC: 8953 AN: 1383872 Hom.: 41 Cov.: 30 AF XY: 0.00650 AC XY: 4440 AN XY: 682870

Gnomad4 AFR exome AF: 0.000728

Gnomad4 AMR exome AF: 0.00269

Gnomad4 ASJ exome AF: 0.00365

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00274

Gnomad4 FIN exome AF: 0.00513

Gnomad4 NFE exome AF: 0.00743

Gnomad4 OTH exome AF: 0.00562

GnomAD4 genome AF: 0.00456 AC: 695 AN: 152318 Hom.: 2 Cov.: 32 AF XY: 0.00435 AC XY: 324 AN XY: 74486

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.00775

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00581 Hom.: 0

Bravo AF: 0.00412

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	Jun 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.0020
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: rs189473926; hg19: chr11-111412284;