rs2514527

Positions:

• chr8-96157099-C-A
• chr8-96157099-C-T

Variant summary

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

The NM_001001557.4(GDF6):​c.406+3188G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,096 control chromosomes in the GnomAD database, including 31,696 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 0.63 (31696 hom., cov: 33)
• Consequence: GDF6 NM_001001557.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290

Genes affected

GDF6 (HGNC:4221): (growth differentiation factor 6) 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 protein is required for normal formation of some bones and joints in the limbs, skull, and axial skeleton. Mutations in this gene are associated with Klippel-Feil syndrome, microphthalmia, and Leber congenital amaurosis. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF6	NM_001001557.4	c.406+3188G>T		intron_variant		ENST00000287020.7	NP_001001557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF6	ENST00000287020.7	c.406+3188G>T		intron_variant		1	NM_001001557.4	ENSP00000287020	P1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96193 AN: 151978 Hom.: 31656 Cov.: 33

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.633 AC: 96286 AN: 152096 Hom.: 31696 Cov.: 33 AF XY: 0.625 AC XY: 46448 AN XY: 74352

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.620

Alfa AF: 0.624 Hom.: 47615

Bravo AF: 0.627

Asia WGS AF: 0.443 AC: 1545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.62

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: rs2514527; hg19: chr8-97169327;