10-69096216-A-T

Position:

• chr10-69096216-A-T

Variant summary

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

The NM_002727.4(SRGN):​c.80-868A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,950 control chromosomes in the GnomAD database, including 15,275 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 0.42 (15275 hom., cov: 32)
• Consequence: SRGN NM_002727.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGN	NM_002727.4	c.80-868A>T		intron_variant		ENST00000242465.4	NP_002718.2
SRGN	NM_001321053.2	c.80-868A>T		intron_variant			NP_001307982.1
SRGN	NM_001321054.1	c.60-7655A>T		intron_variant			NP_001307983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGN	ENST00000242465.4	c.80-868A>T		intron_variant		1	NM_002727.4	ENSP00000242465	P1
SRGN	ENST00000462445.1	n.132-7655A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63558 AN: 151832 Hom.: 15286 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.418 AC: 63547 AN: 151950 Hom.: 15275 Cov.: 32 AF XY: 0.417 AC XY: 30967 AN XY: 74258

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.486

Alfa AF: 0.478 Hom.: 2335

Bravo AF: 0.406

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.41
DANN	Benign	0.65

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: rs2855025; hg19: chr10-70855972;