dbSNP rs2657880: SPRYD4:c.*409G>C (chr12-56469986-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.308

Publications

36 publications found

Variant links:

Genes affected

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

SPRYD4 links:

ENSG00000285528 (HGNC:):

ENSG00000285528 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRYD4	NM_207344.4 link	c.*409G>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000338146.7	NP_997227.1	Q8WW59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRYD4	ENST00000338146.7 link	c.*409G>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_207344.4	ENSP00000338034.5		Q8WW59
ENSG00000285528	ENST00000648304.1 link	n.183-16231C>G		intron_variant	Intron 1 of 3			ENSP00000497190.1		A0A3B3IS89

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23074

AN:

152104

Hom.:

2041

Cov.:

show subpopulations

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.:

AF XY:

0.147

AC XY:

2170

AN XY:

14774

show subpopulations

African (AFR)

AF:

0.0449

AC:

AN:

1292

American (AMR)

AF:

0.204

AC:

675

AN:

3304

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

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:

AN:

European-Non Finnish (NFE)

AF:

0.160

AC:

2363

AN:

14774

Other (OTH)

AF:

0.149

AC:

194

AN:

1302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

160

321

481

642

802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.152

AC:

23095

AN:

152222

Hom.:

2049

Cov.:

AF XY:

0.153

AC XY:

11410

AN XY:

74424

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12628

AN:

67994

Other (OTH)

AF:

0.168

AC:

354

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

994

1987

2981

3974

4968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.66

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over