rs2657880

Positions:

• chr12-56469986-G-C

Variant summary

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

The NM_207344.4(SPRYD4):​c.*409G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 180,158 control chromosomes in the GnomAD database, including 2,447 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 0.15 (2049 hom., cov: 32)
  • Exomes 𝑓: 0.15 (398 hom.)
• Consequence: SPRYD4 NM_207344.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

Genes affected

SPRYD4 (HGNC:27468): (SPRY domain containing 4) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285528 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRYD4	NM_207344.4	c.*409G>C		3_prime_UTR_variant	2/2	ENST00000338146.7	NP_997227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRYD4	ENST00000338146.7	c.*409G>C		3_prime_UTR_variant	2/2	1	NM_207344.4	ENSP00000338034.5
ENSG00000285528	ENST00000648304.1	n.183-16231C>G		intron_variant				ENSP00000497190.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23074 AN: 152104 Hom.: 2041 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0903

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.148 AC: 4134 AN: 27936 Hom.: 398 Cov.: 0 AF XY: 0.147 AC XY: 2170 AN XY: 14774

Gnomad4 AFR exome AF: 0.0449

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.0668

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.152 AC: 23095 AN: 152222 Hom.: 2049 Cov.: 32 AF XY: 0.153 AC XY: 11410 AN XY: 74424

Gnomad4 AFR AF: 0.0676

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0900

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.168

Alfa AF: 0.163 Hom.: 295

Bravo AF: 0.149

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2657880; hg19: chr12-56863770; COSMIC: COSV57666258; COSMIC: COSV57666258;