Variant 5-142314111-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001127496.3(SPRY4):c.*98G>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 0.00497 in 1,337,840 control chromosomes in the GnomAD database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 132 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 118 hom. )

Consequence

SPRY4
NM_001127496.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.462

Variant links:

Genes affected

SPRY4 (HGNC:15533): (sprouty RTK signaling antagonist 4) This gene encodes a member of a family of cysteine- and proline-rich proteins. The encoded protein is an inhibitor of the receptor-transduced mitogen-activated protein kinase (MAPK) signaling pathway. Activity of this protein impairs the formation of active GTP-RAS. Nucleotide variation in this gene has been associated with hypogonadotropic hypogonadism 17 with or without anosmia. Alternative splicing results in a multiple transcript variants. [provided by RefSeq, Jun 2014]

SPRY4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-142314111-C-G is Benign according to our data. Variant chr5-142314111-C-G is described in ClinVar as [Benign]. Clinvar id is 1227299.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRY4	NM_001127496.3 link	c.*98G>C		3_prime_UTR_variant	2/2	ENST00000434127.3	NP_001120968.1	Q9C004-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPRY4	ENST00000434127 link	c.*98G>C	3_prime_UTR_variant	2/2	1	NM_001127496.3	ENSP00000399468.2	Q9C004-1
SPRY4	ENST00000344120 link	c.*98G>C	3_prime_UTR_variant	3/3	1		ENSP00000344967.4	A0A0C4DFS6
SPRY4	ENST00000643792.1 link	n.1680G>C	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3549

AN:

152164

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0806

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0139

GnomAD4 exome

AF:

0.00261

AC:

3095

AN:

1185558

Hom.:

118

Cov.:

AF XY:

0.00226

AC XY:

1318

AN XY:

582386

show subpopulations

Gnomad4 AFR exome

AF:

0.0844

Gnomad4 AMR exome

AF:

0.00674

Gnomad4 ASJ exome

AF:

0.000989

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000458

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000273

Gnomad4 OTH exome

AF:

0.00585

GnomAD4 genome

AF:

0.0234

AC:

3556

AN:

152282

Hom.:

132

Cov.:

AF XY:

0.0218

AC XY:

1625

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.00935

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0276

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.7

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over