chr11-111540883-G-A

Variant names:

• chr11-111540883-G-A
• rs11213935
• NM_178834.5:c.40G>A

Variant summary

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

The NM_001258391.2(LAYN):​c.-238G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00984 in 1,532,362 control chromosomes in the GnomAD database, including 1,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (618 hom., cov: 33)
  • Exomes 𝑓: 0.0055 (561 hom.)
• Consequence: LAYN NM_001258391.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.214
• Publications: 8 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012070537).
• BP6: Variant 11-111540883-G-A is Benign according to our data. Variant chr11-111540883-G-A is described in ClinVar as Benign. ClinVar VariationId is 768483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258391.2. 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
	LAYN	NM_178834.5	MANE Select	c.40G>A	p.Val14Met	missense	Exon 1 of 7	NP_849156.1	Q6UX15-2
	LAYN	NM_001258391.2		c.-238G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001245320.1	Q6UX15-3
	LAYN	NM_001258390.2		c.40G>A	p.Val14Met	missense	Exon 1 of 8	NP_001245319.1	Q6UX15-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAYN	ENST00000375614.7	TSL:1 MANE Select	c.40G>A	p.Val14Met	missense	Exon 1 of 7	ENSP00000364764.2	Q6UX15-2
	LAYN	ENST00000375615.7	TSL:1	c.40G>A	p.Val14Met	missense	Exon 1 of 8	ENSP00000364765.3	Q6UX15-1
	LAYN	ENST00000436913.6	TSL:2	c.-238G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000392942.2	Q6UX15-3

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7462 AN: 152198 Hom.: 615 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0349

GnomAD2 exomes AF: 0.0109 AC: 1405 AN: 128318 AF XY: 0.00840

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.00732

Gnomad ASJ exome AF: 0.00623

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000178

Gnomad NFE exome AF: 0.000972

Gnomad OTH exome AF: 0.00726

GnomAD4 exome AF: 0.00550 AC: 7584 AN: 1380056 Hom.: 561 Cov.: 31 AF XY: 0.00477 AC XY: 3251 AN XY: 680954

African (AFR) AF: 0.177 AC: 5544 AN: 31392

American (AMR) AF: 0.00924 AC: 329 AN: 35598

Ashkenazi Jewish (ASJ) AF: 0.00447 AC: 112 AN: 25072

East Asian (EAS) AF: 0.00 AC: 0 AN: 35624

South Asian (SAS) AF: 0.000481 AC: 38 AN: 78992

European-Finnish (FIN) AF: 0.000414 AC: 14 AN: 33788

Middle Eastern (MID) AF: 0.0128 AC: 55 AN: 4302

European-Non Finnish (NFE) AF: 0.000706 AC: 761 AN: 1077664

Other (OTH) AF: 0.0127 AC: 731 AN: 57624

GnomAD4 genome AF: 0.0492 AC: 7490 AN: 152306 Hom.: 618 Cov.: 33 AF XY: 0.0477 AC XY: 3553 AN XY: 74466

African (AFR) AF: 0.169 AC: 7024 AN: 41558

American (AMR) AF: 0.0192 AC: 294 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 68030

Other (OTH) AF: 0.0346 AC: 73 AN: 2112

Alfa AF: 0.0359 Hom.: 94

Bravo AF: 0.0559

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ExAC AF: 0.0101 AC: 230

Asia WGS AF: 0.0110 AC: 38 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.1
DANN	Benign	0.85
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.21
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.024
Sift	Benign	0.14	T
Sift4G	Benign	0.28	T
Polyphen		0.0070	B
Vest4		0.077
MPC		0.082
ClinPred		0.0023	T
GERP RS		-0.90
PromoterAI		0.064	Neutral
Varity_R		0.036
gMVP		0.48
Mutation Taster		=99/1	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: rs11213935; hg19: chr11-111411608;