Variant chr5-142314028-C-T 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.*181G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 651,562 control chromosomes in the GnomAD database, including 189,501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.70 ( 38728 hom., cov: 32)

Exomes 𝑓: 0.77 ( 150773 hom. )

Consequence

SPRY4
NM_001127496.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.871

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 5-142314028-C-T is Benign according to our data. Variant chr5-142314028-C-T is described in ClinVar as [Benign]. Clinvar id is 1292770.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRY4	NM_001127496.3 link	c.*181G>A		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.*181G>A	3_prime_UTR_variant	2/2	1	NM_001127496.3	ENSP00000399468.2	Q9C004-1
SPRY4	ENST00000344120 link	c.*181G>A	3_prime_UTR_variant	3/3	1		ENSP00000344967.4	A0A0C4DFS6
SPRY4	ENST00000643792.1 link	n.1763G>A	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.701

AC:

106558

AN:

151956

Hom.:

38700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.776

Gnomad AMR

AF:

0.786

Gnomad ASJ

AF:

0.821

Gnomad EAS

AF:

0.918

Gnomad SAS

AF:

0.788

Gnomad FIN

AF:

0.739

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.738

GnomAD4 exome

AF:

0.774

AC:

386445

AN:

499488

Hom.:

150773

Cov.:

AF XY:

0.775

AC XY:

199701

AN XY:

257764

show subpopulations

Gnomad4 AFR exome

AF:

0.495

Gnomad4 AMR exome

AF:

0.815

Gnomad4 ASJ exome

AF:

0.813

Gnomad4 EAS exome

AF:

0.907

Gnomad4 SAS exome

AF:

0.774

Gnomad4 FIN exome

AF:

0.731

Gnomad4 NFE exome

AF:

0.774

Gnomad4 OTH exome

AF:

0.764

GnomAD4 genome

AF:

0.701

AC:

106626

AN:

152074

Hom.:

38728

Cov.:

AF XY:

0.704

AC XY:

52324

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.787

Gnomad4 ASJ

AF:

0.821

Gnomad4 EAS

AF:

0.919

Gnomad4 SAS

AF:

0.788

Gnomad4 FIN

AF:

0.739

Gnomad4 NFE

AF:

0.771

Gnomad4 OTH

AF:

0.742

Alfa

AF:

0.766

Hom.:

73368

Bravo

AF:

0.696

Asia WGS

AF:

0.797

AC:

2772

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

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.1

DANN

Benign

0.61

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