chr1-152600927-C-A

Variant names:

• chr1-152600927-C-A
• rs768103728
• NM_178434.3:c.196C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_178434.3(LCE3C):​c.196C>A​(p.Arg66Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000082 in 854,020 control chromosomes in the GnomAD database, including 1 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: not found (cov: 16)
  • Exomes 𝑓: 0.0000082 (1 hom.)
• Consequence: LCE3C NM_178434.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 1 publications found

Genes affected

LCE3C (HGNC:16612): (late cornified envelope 3C) Involved in defense response to Gram-negative bacterium; defense response to Gram-positive bacterium; and killing of cells of other organism. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-2.07 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178434.3. 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
	LCE3C	NM_178434.3	MANE Select	c.196C>A	p.Arg66Arg	synonymous	Exon 2 of 2	NP_848521.1	Q5T5A8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE3C	ENST00000684028.1	MANE Select	c.196C>A	p.Arg66Arg	synonymous	Exon 2 of 2	ENSP00000507204.1	Q5T5A8
	LCE3C	ENST00000333881.3	TSL:6	c.196C>A	p.Arg66Arg	synonymous	Exon 1 of 1	ENSP00000334644.3	Q5T5A8

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD2 exomes AF: 0.0000264 AC: 4 AN: 151384 AF XY: 0.0000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000357

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000820 AC: 7 AN: 854020 Hom.: 1 Cov.: 27 AF XY: 0.00000236 AC XY: 1 AN XY: 424492

African (AFR) AF: 0.00 AC: 0 AN: 27576

American (AMR) AF: 0.00 AC: 0 AN: 26850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15856

East Asian (EAS) AF: 0.000198 AC: 5 AN: 25248

South Asian (SAS) AF: 0.00 AC: 0 AN: 50944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3662

European-Non Finnish (NFE) AF: 0.00000157 AC: 1 AN: 637160

Other (OTH) AF: 0.0000275 AC: 1 AN: 36396

GnomAD4 genome Cov.: 16

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.0
DANN	Benign	0.48
PhyloP100		-2.1
PromoterAI		-0.019	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs768103728; hg19: chr1-152573403;