rs7443175

Variant names:

• chr5-142315884-T-C
• rs7443175
• NM_001127496.3:c.-47-729A>G

Variant summary

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

The NM_001127496.3(SPRY4):​c.-47-729A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,150 control chromosomes in the GnomAD database, including 35,979 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 0.66 (35973 hom., cov: 33)
  • Exomes 𝑓: 0.77 (6 hom.)
• Consequence: SPRY4 NM_001127496.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRY4	NM_001127496.3	c.-47-729A>G		intron_variant	Intron 1 of 1	ENST00000434127.3	NP_001120968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRY4	ENST00000434127.3	c.-47-729A>G		intron_variant	Intron 1 of 1	1	NM_001127496.3	ENSP00000399468.2

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100810 AN: 152010 Hom.: 35952 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.706

GnomAD4 exome AF: 0.773 AC: 17 AN: 22 Hom.: 6 AF XY: 0.800 AC XY: 8 AN XY: 10

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.714

GnomAD4 genome AF: 0.663 AC: 100849 AN: 152128 Hom.: 35973 Cov.: 33 AF XY: 0.667 AC XY: 49646 AN XY: 74382

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.711

Alfa AF: 0.739 Hom.: 19313

Bravo AF: 0.653

Asia WGS AF: 0.779 AC: 2709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7443175; hg19: chr5-141695449;