17-44347231-G-C

Position:

• chr17-44347231-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002087.4(GRN):​c.-8+1897G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,084 control chromosomes in the GnomAD database, including 18,001 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 0.46 (18001 hom., cov: 31)
• Consequence: GRN NM_002087.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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]

GRN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRN	NM_002087.4	c.-8+1897G>C		intron_variant		ENST00000053867.8	NP_002078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRN	ENST00000053867.8	c.-8+1897G>C		intron_variant		1	NM_002087.4	ENSP00000053867.2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70092 AN: 151966 Hom.: 17947 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.462 AC: 70206 AN: 152084 Hom.: 18001 Cov.: 31 AF XY: 0.472 AC XY: 35093 AN XY: 74356

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.915

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.445

Alfa AF: 0.396 Hom.: 1642

Bravo AF: 0.475

Asia WGS AF: 0.767 AC: 2665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.60
DANN	Benign	0.36

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: rs4792938; hg19: chr17-42424599;