10-47312116-A-G

Variant names:

• chr10-47312116-A-G
• rs762454
• NM_004962.5:c.1246-485A>G

Variant summary

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

The NM_004962.5(GDF10):​c.1246-485A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,078 control chromosomes in the GnomAD database, including 9,090 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 0.34 (9090 hom., cov: 33)
• Consequence: GDF10 NM_004962.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• Publications: 14 publications found

Genes affected

GDF10 (HGNC:4215): (growth differentiation factor 10) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This promotes neural repair after stroke. Additionally, this protein may act as a tumor suppressor and reduced expression of this gene is associated with oral cancer. [provided by RefSeq, Jul 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF10	NM_004962.5	c.1246-485A>G		intron_variant	Intron 2 of 2	ENST00000580279.2	NP_004953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF10	ENST00000580279.2	c.1246-485A>G		intron_variant	Intron 2 of 2	1	NM_004962.5	ENSP00000464145.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52365 AN: 151960 Hom.: 9085 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.345 AC: 52413 AN: 152078 Hom.: 9090 Cov.: 33 AF XY: 0.345 AC XY: 25667 AN XY: 74334

African (AFR) AF: 0.384 AC: 15937 AN: 41476

American (AMR) AF: 0.274 AC: 4188 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3470

East Asian (EAS) AF: 0.340 AC: 1757 AN: 5166

South Asian (SAS) AF: 0.380 AC: 1833 AN: 4818

European-Finnish (FIN) AF: 0.368 AC: 3894 AN: 10578

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22581 AN: 67960

Other (OTH) AF: 0.335 AC: 707 AN: 2110

Alfa AF: 0.334 Hom.: 24709

Bravo AF: 0.338

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.48
PhyloP100		0.17

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

Other links and lift over

dbSNP: rs762454; hg19: chr10-48427246;