10-69102220-A-G

Variant names:

• chr10-69102220-A-G
• rs2805915
• NM_002727.4:c.228-1651A>G

Variant summary

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

The NM_002727.4(SRGN):​c.228-1651A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,850 control chromosomes in the GnomAD database, including 18,157 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 0.47 (18157 hom., cov: 31)
• Consequence: SRGN NM_002727.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRGN	NM_002727.4	c.228-1651A>G		intron_variant	Intron 2 of 2	ENST00000242465.4	NP_002718.2
SRGN	NM_001321053.2	c.228-1651A>G		intron_variant	Intron 3 of 3		NP_001307982.1
SRGN	NM_001321054.1	c.60-1651A>G		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.228-1651A>G		intron_variant	Intron 2 of 2	1	NM_002727.4	ENSP00000242465.3
SRGN	ENST00000718456.1	c.228-1651A>G		intron_variant	Intron 2 of 2			ENSP00000520834.1
SRGN	ENST00000462445.1	n.132-1651A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71126 AN: 151732 Hom.: 18167 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.468 AC: 71119 AN: 151850 Hom.: 18157 Cov.: 31 AF XY: 0.467 AC XY: 34641 AN XY: 74218

African (AFR) AF: 0.262 AC: 10836 AN: 41400

American (AMR) AF: 0.490 AC: 7466 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2486 AN: 3464

East Asian (EAS) AF: 0.396 AC: 2041 AN: 5148

South Asian (SAS) AF: 0.483 AC: 2330 AN: 4820

European-Finnish (FIN) AF: 0.490 AC: 5163 AN: 10540

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38978 AN: 67916

Other (OTH) AF: 0.538 AC: 1137 AN: 2112

Alfa AF: 0.543 Hom.: 75661

Bravo AF: 0.460

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		0.019
Mutation Taster		=100/0	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: rs2805915; hg19: chr10-70861976;