Genetic Variant SPRY1:c.*32T>C (chr4-123402583-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001258038.2(SPRY1):c.*32T>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 0.634 in 1,544,964 control chromosomes in the GnomAD database, including 320,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 24469 hom., cov: 32)

Exomes 𝑓: 0.64 ( 296128 hom. )

Consequence

SPRY1
NM_001258038.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.511

Publications

19 publications found

Variant links:

Genes affected

SPRY1 (HGNC:11269): (sprouty RTK signaling antagonist 1) Involved in negative regulation of fibroblast growth factor receptor signaling pathway. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPRY1 Gene-Disease associations (from GenCC):

craniosynostosis
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

SPRY1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-123402583-T-C is Benign according to our data. Variant chr4-123402583-T-C is described in ClinVar as Benign. ClinVar VariationId is 1270466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258038.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPRY1	NM_001258038.2	MANE Select	c.*32T>C	3_prime_UTR	Exon 3 of 3	NP_001244967.1	O43609
SPRY1	NM_001258039.1		c.*32T>C	3_prime_UTR	Exon 2 of 2	NP_001244968.1	O43609
SPRY1	NM_001375410.1		c.*32T>C	3_prime_UTR	Exon 3 of 3	NP_001362339.1	O43609

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPRY1	ENST00000651917.1	MANE Select	c.*32T>C	3_prime_UTR	Exon 3 of 3	ENSP00000498292.1	O43609
SPRY1	ENST00000339241.1	TSL:1	c.*32T>C	3_prime_UTR	Exon 2 of 2	ENSP00000343785.1	O43609
SPRY1	ENST00000394339.2	TSL:1	c.*32T>C	3_prime_UTR	Exon 2 of 2	ENSP00000377871.2	O43609

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81798

AN:

151938

Hom.:

24464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.587

Gnomad AMR

AF:

0.540

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.685

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.679

Gnomad OTH

AF:

0.554

GnomAD2 exomes

AF:

0.582

AC:

120404

AN:

206964

AF XY:

0.588

show subpopulations

Gnomad AFR exome

AF:

0.271

Gnomad AMR exome

AF:

0.477

Gnomad ASJ exome

AF:

0.663

Gnomad EAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.690

Gnomad NFE exome

AF:

0.672

Gnomad OTH exome

AF:

0.629

GnomAD4 exome

AF:

0.645

AC:

897896

AN:

1392908

Hom.:

296128

Cov.:

AF XY:

0.641

AC XY:

439175

AN XY:

685550

show subpopulations

African (AFR)

AF:

0.263

AC:

8017

AN:

30512

American (AMR)

AF:

0.479

AC:

14977

AN:

31264

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

14981

AN:

22650

East Asian (EAS)

AF:

0.403

AC:

15660

AN:

38824

South Asian (SAS)

AF:

0.461

AC:

35510

AN:

76962

European-Finnish (FIN)

AF:

0.691

AC:

35659

AN:

51612

Middle Eastern (MID)

AF:

0.560

AC:

3018

AN:

5392

European-Non Finnish (NFE)

AF:

0.681

AC:

734963

AN:

1078566

Other (OTH)

AF:

0.615

AC:

35111

AN:

57126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

15397

30794

46192

61589

76986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19084

38168

57252

76336

95420

<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:

0.538

AC:

81815

AN:

152056

Hom.:

24469

Cov.:

AF XY:

0.536

AC XY:

39826

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.282

AC:

11693

AN:

41470

American (AMR)

AF:

0.540

AC:

8244

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

2293

AN:

3468

East Asian (EAS)

AF:

0.428

AC:

2220

AN:

5182

South Asian (SAS)

AF:

0.433

AC:

2086

AN:

4816

European-Finnish (FIN)

AF:

0.685

AC:

7241

AN:

10566

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.679

AC:

46174

AN:

67966

Other (OTH)

AF:

0.557

AC:

1172

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1738

3477

5215

6954

8692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.617

Hom.:

57573

Bravo

AF:

0.517

Asia WGS

AF:

0.414

AC:

1438

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

8.7

(source)

DANN

Benign

0.61

PhyloP100

-0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over