dbSNP rs2853208: GFRA4:p.Pro237Pro (chr20-3660176-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_022139.4(GFRA4):c.711G>T(p.Pro237Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GFRA4
NM_022139.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0770

Publications

13 publications found

Variant links:

Genes affected

GFRA4 (HGNC:13821): (GDNF family receptor alpha 4) The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for persephin, and mediates activation of the RET tyrosine kinase receptor. This gene is a candidate gene for RET-associated diseases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

GFRA4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP7

Synonymous conserved (PhyloP=0.077 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFRA4	NM_022139.4 link	c.711G>T	p.Pro237Pro	synonymous_variant	Exon 5 of 6	ENST00000290417.7	NP_071422.1	Q9GZZ7-2
GFRA4	NM_145762.3 link	c.801G>T	p.Pro267Pro	synonymous_variant	Exon 4 of 5		NP_665705.1	Q9GZZ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFRA4	ENST00000290417.7 link	c.711G>T	p.Pro237Pro	synonymous_variant	Exon 5 of 6	1	NM_022139.4	ENSP00000290417.2		Q9GZZ7-2
GFRA4	ENST00000319242.8 link	c.801G>T	p.Pro267Pro	synonymous_variant	Exon 4 of 5	1		ENSP00000313423.3		Q9GZZ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1440638

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714970

African (AFR)

AF:

0.00

AC:

AN:

33010

American (AMR)

AF:

0.00

AC:

AN:

41048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25422

East Asian (EAS)

AF:

0.00

AC:

AN:

39308

South Asian (SAS)

AF:

0.00

AC:

AN:

82876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5230

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102522

Other (OTH)

AF:

0.00

AC:

AN:

59368

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.8

(source)

DANN

Benign

0.62

PhyloP100

0.077

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over