rs6701216

Variant names:

• chr1-152806050-C-T
• rs6701216
• NM_178351.4:c.-21+551G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178351.4(LCE1C):​c.-21+551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,070 control chromosomes in the GnomAD database, including 3,781 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3781 hom., cov: 32)
• Consequence: LCE1C NM_178351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835
• Publications: 17 publications found

Genes affected

LCE1C (HGNC:29464): (late cornified envelope 1C) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE1C	NM_178351.4	c.-21+551G>A		intron_variant	Intron 1 of 1	ENST00000607093.2	NP_848128.1
LCE1C	NM_001276331.2	c.-21+551G>A		intron_variant	Intron 1 of 2		NP_001263260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE1C	ENST00000607093.2	c.-21+551G>A		intron_variant	Intron 1 of 1	6	NM_178351.4	ENSP00000475270.1
LCE1C	ENST00000606576.1	c.-21+551G>A		intron_variant	Intron 1 of 2	3		ENSP00000476034.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31887 AN: 151952 Hom.: 3759 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 31947 AN: 152070 Hom.: 3781 Cov.: 32 AF XY: 0.215 AC XY: 16011 AN XY: 74334

African (AFR) AF: 0.283 AC: 11744 AN: 41450

American (AMR) AF: 0.257 AC: 3938 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3466

East Asian (EAS) AF: 0.334 AC: 1726 AN: 5164

South Asian (SAS) AF: 0.300 AC: 1443 AN: 4808

European-Finnish (FIN) AF: 0.170 AC: 1801 AN: 10576

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10053 AN: 67988

Other (OTH) AF: 0.232 AC: 490 AN: 2116

Alfa AF: 0.172 Hom.: 4707

Bravo AF: 0.218

Asia WGS AF: 0.347 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6701216; hg19: chr1-152778526;