chr12-75410455-C-A

Variant names:

• chr12-75410455-C-A
• rs142539769
• NM_001270396.2:c.256C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_001270396.2(GLIPR1L2):​c.256C>A​(p.Arg86Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,442,666 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: GLIPR1L2 NM_001270396.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• Publications: 1 publications found

Genes affected

GLIPR1L2 (HGNC:28592): (GLIPR1 like 2) This gene encodes a member of the cysteine-rich secretory protein, antigen 5, and pathogenesis-related 1 superfamily. Members of this family have roles in a variety of processes, including cancer and immune defense. This gene is located in a cluster with two related genes on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP7: Synonymous conserved (PhyloP=0.469 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270396.2. 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
	GLIPR1L2	NM_001270396.2	MANE Select	c.256C>A	p.Arg86Arg	synonymous	Exon 2 of 6	NP_001257325.1	Q4G1C9-1
	GLIPR1L2	NM_152436.3		c.256C>A	p.Arg86Arg	synonymous	Exon 2 of 4	NP_689649.1	Q4G1C9-2
	GLIPR1L2	NR_072995.2		n.414C>A		non_coding_transcript_exon	Exon 3 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIPR1L2	ENST00000550916.6	TSL:1 MANE Select	c.256C>A	p.Arg86Arg	synonymous	Exon 2 of 6	ENSP00000448248.1	Q4G1C9-1
	GLIPR1L2	ENST00000320460.8	TSL:1	c.256C>A	p.Arg86Arg	synonymous	Exon 2 of 4	ENSP00000317385.4	Q4G1C9-2
	GLIPR1L2	ENST00000378692.7	TSL:1	c.-66C>A		5_prime_UTR	Exon 3 of 7	ENSP00000367963.3	Q4G1C9-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000826 AC: 2 AN: 242048 AF XY: 0.00000760

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000624 AC: 9 AN: 1442666 Hom.: 0 Cov.: 30 AF XY: 0.00000698 AC XY: 5 AN XY: 716834

African (AFR) AF: 0.00 AC: 0 AN: 32824

American (AMR) AF: 0.00 AC: 0 AN: 42328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25550

East Asian (EAS) AF: 0.00 AC: 0 AN: 39036

South Asian (SAS) AF: 0.0000960 AC: 8 AN: 83296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101648

Other (OTH) AF: 0.0000168 AC: 1 AN: 59446

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	9.7
DANN	Benign	0.63
PhyloP100		0.47
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142539769; hg19: chr12-75804235;