NM_014357.5:c.194A>G

Variant names:

• chr1-152687037-A-G
• rs575837944
• NM_014357.5:c.194A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014357.5(LCE2B):​c.194A>G​(p.Asn65Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,461,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LCE2B NM_014357.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.877
• Publications: 0 publications found

Genes affected

LCE2B (HGNC:16610): (late cornified envelope 2B) This gene is one of the at least 20 genes expressed during epidermal differentiation and located on chromosomal band 1q21. This gene is involved in epidermal differentiation, and it is expressed at high levels in normal and psoriatic skin, but not in cultured keratinocytes or in any other tested cell types or tissues. [provided by RefSeq, Jul 2008]

ENSG00000304363 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015746623).
• BP6: Variant 1-152687037-A-G is Benign according to our data. Variant chr1-152687037-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3537500.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014357.5. 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
	LCE2B	NM_014357.5	MANE Select	c.194A>G	p.Asn65Ser	missense	Exon 2 of 2	NP_055172.1	O14633

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE2B	ENST00000368780.4	TSL:1 MANE Select	c.194A>G	p.Asn65Ser	missense	Exon 2 of 2	ENSP00000357769.3	O14633
	ENSG00000304363	ENST00000802896.1		n.81-8520T>C		intron	N/A
	ENSG00000304363	ENST00000802897.1		n.69-20311T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 4 AN: 149156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

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: 0.0000296

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251264 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000308 AC: 45 AN: 1461148 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 726944

African (AFR) AF: 0.0000303 AC: 1 AN: 33032

American (AMR) AF: 0.000134 AC: 6 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111862

Other (OTH) AF: 0.0000166 AC: 1 AN: 60316

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000268 AC: 4 AN: 149266 Hom.: 0 Cov.: 32 AF XY: 0.0000274 AC XY: 2 AN XY: 72906

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000251 AC: 1 AN: 39828

American (AMR) AF: 0.0000663 AC: 1 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5062

South Asian (SAS) AF: 0.00 AC: 0 AN: 4690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67466

Other (OTH) AF: 0.00 AC: 0 AN: 2080

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000108036), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.24
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.88
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.049
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MVP		0.14
MPC		0.0033
ClinPred		0.028	T
GERP RS		0.72
Varity_R		0.019
gMVP		0.011
Mutation Taster		=99/1	polymorphism

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: rs575837944; hg19: chr1-152659513; COSMIC: COSV64227423;