rs17473271

Variant names:

• chr10-69089146-G-A
• rs17473271
• NM_002727.4:c.79+910G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002727.4(SRGN):​c.79+910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,090 control chromosomes in the GnomAD database, including 3,307 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 0.19 (3307 hom., cov: 32)
• Consequence: SRGN NM_002727.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 3 publications found

Genes affected

SRGN (HGNC:9361): (serglycin) This gene encodes a protein best known as a hematopoietic cell granule proteoglycan. Proteoglycans stored in the secretory granules of many hematopoietic cells also contain a protease-resistant peptide core, which may be important for neutralizing hydrolytic enzymes. This encoded protein was found to be associated with the macromolecular complex of granzymes and perforin, which may serve as a mediator of granule-mediated apoptosis. Two transcript variants, only one of them protein-coding, have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRGN	NM_002727.4	c.79+910G>A		intron_variant	Intron 1 of 2	ENST00000242465.4	NP_002718.2
SRGN	NM_001321053.2	c.79+910G>A		intron_variant	Intron 2 of 3		NP_001307982.1
SRGN	NM_001321054.1	c.59+910G>A		intron_variant	Intron 1 of 1		NP_001307983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRGN	ENST00000242465.4	c.79+910G>A		intron_variant	Intron 1 of 2	1	NM_002727.4	ENSP00000242465.3
SRGN	ENST00000718456.1	c.79+910G>A		intron_variant	Intron 1 of 2			ENSP00000520834.1
SRGN	ENST00000462445.1	n.131+910G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28568 AN: 151972 Hom.: 3301 Cov.: 32

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.188 AC: 28594 AN: 152090 Hom.: 3307 Cov.: 32 AF XY: 0.191 AC XY: 14170 AN XY: 74336

African (AFR) AF: 0.0869 AC: 3608 AN: 41502

American (AMR) AF: 0.147 AC: 2242 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3468

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5182

South Asian (SAS) AF: 0.140 AC: 675 AN: 4820

European-Finnish (FIN) AF: 0.366 AC: 3856 AN: 10544

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16870 AN: 67978

Other (OTH) AF: 0.172 AC: 363 AN: 2114

Alfa AF: 0.189 Hom.: 995

Bravo AF: 0.167

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.6
DANN	Benign	0.84
PhyloP100		0.11
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17473271; hg19: chr10-70848902;