5-142321387-A-G

Position:

• chr5-142321387-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127496.3(SPRY4):​c.-48+3457T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,184 control chromosomes in the GnomAD database, including 48,959 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 0.80 (48959 hom., cov: 32)
• Consequence: SPRY4 NM_001127496.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPRY4	NM_001127496.3	c.-48+3457T>C		intron_variant		ENST00000434127.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRY4	ENST00000434127.3	c.-48+3457T>C		intron_variant		1	NM_001127496.3	P1
SPRY4	ENST00000344120.4	c.-29-1593T>C		intron_variant		1
SPRY4	ENST00000511815.1	c.-109-1593T>C		intron_variant		4
SPRY4	ENST00000503582.1	n.528+2503T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121675 AN: 152066 Hom.: 48904 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.791

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.800 AC: 121786 AN: 152184 Hom.: 48959 Cov.: 32 AF XY: 0.803 AC XY: 59713 AN XY: 74398

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.794

Alfa AF: 0.771 Hom.: 59589

Bravo AF: 0.807

Asia WGS AF: 0.891 AC: 3099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.57

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: rs6897690; hg19: chr5-141700952; COSMIC: COSV59985586; COSMIC: COSV59985586;