rs4792939

Positions:

• chr17-44347945-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002087.4(GRN):​c.-7-1213G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.57 (11796 hom., cov: 16)
  • Failed GnomAD Quality Control
• Consequence: GRN NM_002087.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

GRN (HGNC:4601): (granulin precursor) Granulins are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and PC cell-derived growth factor. Cleavage of the signal peptide produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively. Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRN	NM_002087.4	c.-7-1213G>A		intron_variant		ENST00000053867.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRN	ENST00000053867.8	c.-7-1213G>A		intron_variant		1	NM_002087.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 54354 AN: 95818 Hom.: 11799 Cov.: 16 FAILED QC

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.575

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.567 AC: 54353 AN: 95888 Hom.: 11796 Cov.: 16 AF XY: 0.565 AC XY: 25671 AN XY: 45460

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.570

Alfa AF: 0.799 Hom.: 36326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs4792939; hg19: chr17-42425313; COSMIC: COSV50007835; COSMIC: COSV50007835;