5-142314028-C-T

Position:

• chr5-142314028-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.871

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]

ACMG classification

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	UniProt
SPRY4	NM_001127496.3	c.*181G>A		3_prime_UTR_variant	2/2	ENST00000434127.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRY4	ENST00000434127.3	c.*181G>A		3_prime_UTR_variant	2/2	1	NM_001127496.3	P1
SPRY4	ENST00000344120.4	c.*181G>A		3_prime_UTR_variant	3/3	1
SPRY4	ENST00000643792.1	n.1763G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106558 AN: 151956 Hom.: 38700 Cov.: 32

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.: 6 AF XY: 0.775 AC XY: 199701 AN XY: 257764

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.: 32 AF XY: 0.704 AC XY: 52324 AN XY: 74302

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

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

Other links and lift over

dbSNP: rs10040443; hg19: chr5-141693593;