rs180552

Variant names:

• chr10-116059331-G-A
• rs180552
• NM_005264.8:c.*5067C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-116059331-G-A
• chr10-116059331-G-C
• chr10-116059331-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005264.8(GFRA1):​c.*5067C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,036 control chromosomes in the GnomAD database, including 14,014 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 0.39 (14012 hom., cov: 33)
  • Exomes 𝑓: 0.19 (2 hom.)
• Consequence: GFRA1 NM_005264.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 5 publications found

Genes affected

GFRA1 (HGNC:4243): (GDNF family receptor alpha 1) This gene encodes a member of the glial cell line-derived neurotrophic factor receptor (GDNFR) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature receptor. Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. This receptor is a glycosylphosphatidylinositol (GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. This gene is a candidate gene for Hirschsprung disease. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

GFRA1 Gene-Disease associations (from GenCC):

• renal hypodysplasia/aplasia 4

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005264.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA1	NM_005264.8	MANE Select	c.*5067C>T		3_prime_UTR	Exon 11 of 11	NP_005255.1
	GFRA1	NM_001348098.4		c.*5067C>T		3_prime_UTR	Exon 11 of 11	NP_001335027.1
	GFRA1	NM_001145453.4		c.*5067C>T		3_prime_UTR	Exon 10 of 10	NP_001138925.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA1	ENST00000355422.11	TSL:5 MANE Select	c.*5067C>T		3_prime_UTR	Exon 11 of 11	ENSP00000347591.6
	GFRA1	ENST00000369236.5	TSL:1	c.*5067C>T		3_prime_UTR	Exon 9 of 9	ENSP00000358239.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59241 AN: 151896 Hom.: 13972 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.192 AC: 5 AN: 26 Hom.: 2 Cov.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.150 AC: 3 AN: 20

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.390 AC: 59326 AN: 152010 Hom.: 14012 Cov.: 33 AF XY: 0.391 AC XY: 29029 AN XY: 74320

African (AFR) AF: 0.653 AC: 27070 AN: 41448

American (AMR) AF: 0.351 AC: 5359 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3472

East Asian (EAS) AF: 0.613 AC: 3144 AN: 5130

South Asian (SAS) AF: 0.337 AC: 1626 AN: 4826

European-Finnish (FIN) AF: 0.282 AC: 2982 AN: 10576

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.255 AC: 17341 AN: 67960

Other (OTH) AF: 0.391 AC: 826 AN: 2114

Alfa AF: 0.292 Hom.: 12345

Bravo AF: 0.409

Asia WGS AF: 0.482 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.72
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs180552; hg19: chr10-117818842;