rs2074409

Positions:

• chr17-37538240-G-T

Variant summary

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

The NM_007247.6(SYNRG):​c.3517+84C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,010,134 control chromosomes in the GnomAD database, including 44,775 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 0.33 (8977 hom., cov: 32)
  • Exomes 𝑓: 0.27 (35798 hom.)
• Consequence: SYNRG NM_007247.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

Genes affected

SYNRG (HGNC:557): (synergin gamma) This gene encodes a protein that interacts with the gamma subunit of AP1 clathrin-adaptor complex. The AP1 complex is located at the trans-Golgi network and associates specific proteins with clathrin-coated vesicles. This encoded protein may act to connect the AP1 complex to other proteins. Alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNRG	NM_007247.6	c.3517+84C>A		intron_variant		ENST00000612223.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNRG	ENST00000612223.5	c.3517+84C>A		intron_variant		1	NM_007247.6	P4

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49692 AN: 151934 Hom.: 8957 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.275 AC: 235774 AN: 858082 Hom.: 35798 AF XY: 0.275 AC XY: 121133 AN XY: 440046

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.596

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.327 AC: 49754 AN: 152052 Hom.: 8977 Cov.: 32 AF XY: 0.331 AC XY: 24600 AN XY: 74332

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.288

Alfa AF: 0.268 Hom.: 7682

Bravo AF: 0.329

Asia WGS AF: 0.443 AC: 1537 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.1
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2074409; hg19: chr17-35898342;