chr17-44348838-C-G

Position:

• chr17-44348838-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002087.4(GRN):​c.-7-320C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 152,334 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.051 (276 hom., cov: 33)
• Consequence: GRN NM_002087.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.116

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-44348838-C-G is Benign according to our data. Variant chr17-44348838-C-G is described in ClinVar as [Benign]. Clinvar id is 1241013.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRN	NM_002087.4	c.-7-320C>G		intron_variant		ENST00000053867.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRN	ENST00000053867.8	c.-7-320C>G		intron_variant		1	NM_002087.4	P1

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7752 AN: 152216 Hom.: 277 Cov.: 33

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0627

Gnomad OTH AF: 0.0501

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

GnomAD4 genome AF: 0.0509 AC: 7751 AN: 152334 Hom.: 276 Cov.: 33 AF XY: 0.0520 AC XY: 3875 AN XY: 74476

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0626

Gnomad4 OTH AF: 0.0496

Alfa AF: 0.0223 Hom.: 14

Bravo AF: 0.0471

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.62

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: rs78403836; hg19: chr17-42426206;