rs2074409

Variant names:

• chr17-37538240-G-T
• rs2074409
• NM_007247.6:c.3517+84C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SYNRG	NM_007247.6	c.3517+84C>A		intron_variant	Intron 18 of 21	ENST00000612223.5	NP_009178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNRG	ENST00000612223.5	c.3517+84C>A		intron_variant	Intron 18 of 21	1	NM_007247.6	ENSP00000483453.1

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

African (AFR) AF: 0.464 AC: 8955 AN: 19308

American (AMR) AF: 0.263 AC: 6668 AN: 25360

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 4392 AN: 17308

East Asian (EAS) AF: 0.596 AC: 20171 AN: 33866

South Asian (SAS) AF: 0.333 AC: 18767 AN: 56318

European-Finnish (FIN) AF: 0.324 AC: 15797 AN: 48790

Middle Eastern (MID) AF: 0.239 AC: 671 AN: 2808

European-Non Finnish (NFE) AF: 0.243 AC: 149296 AN: 615248

Other (OTH) AF: 0.283 AC: 11057 AN: 39076

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

African (AFR) AF: 0.463 AC: 19190 AN: 41460

American (AMR) AF: 0.254 AC: 3889 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3470

East Asian (EAS) AF: 0.580 AC: 3000 AN: 5170

South Asian (SAS) AF: 0.353 AC: 1701 AN: 4822

European-Finnish (FIN) AF: 0.324 AC: 3417 AN: 10550

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.246 AC: 16747 AN: 67966

Other (OTH) AF: 0.288 AC: 608 AN: 2114

Alfa AF: 0.285 Hom.: 17028

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
PhyloP100		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2074409; hg19: chr17-35898342;