rs2657880

Variant names:

• chr12-56469986-G-C
• rs2657880
• NM_207344.4:c.*409G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 36 publications found

Genes affected

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

ENSG00000285528 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207344.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRYD4	NM_207344.4	MANE Select	c.*409G>C		3_prime_UTR	Exon 2 of 2	NP_997227.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRYD4	ENST00000338146.7	TSL:1 MANE Select	c.*409G>C		3_prime_UTR	Exon 2 of 2	ENSP00000338034.5
	ENSG00000285528	ENST00000648304.1		n.183-16231C>G		intron	N/A	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

African (AFR) AF: 0.0449 AC: 58 AN: 1292

American (AMR) AF: 0.204 AC: 675 AN: 3304

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 80 AN: 564

East Asian (EAS) AF: 0.0668 AC: 155 AN: 2322

South Asian (SAS) AF: 0.130 AC: 418 AN: 3218

European-Finnish (FIN) AF: 0.165 AC: 182 AN: 1100

Middle Eastern (MID) AF: 0.150 AC: 9 AN: 60

European-Non Finnish (NFE) AF: 0.160 AC: 2363 AN: 14774

Other (OTH) AF: 0.149 AC: 194 AN: 1302

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

African (AFR) AF: 0.0676 AC: 2810 AN: 41544

American (AMR) AF: 0.206 AC: 3145 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3472

East Asian (EAS) AF: 0.0900 AC: 466 AN: 5180

South Asian (SAS) AF: 0.148 AC: 716 AN: 4830

European-Finnish (FIN) AF: 0.187 AC: 1977 AN: 10598

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12628 AN: 67994

Other (OTH) AF: 0.168 AC: 354 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.66
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2657880; hg19: chr12-56863770; COSMIC: COSV57666258; COSMIC: COSV57666258;