8-96145563-G-C

Position:

• chr8-96145563-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001001557.4(GDF6):​c.407-39C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,596,918 control chromosomes in the GnomAD database, including 7 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 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (7 hom.)
• Consequence: GDF6 NM_001001557.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BS2: High Homozygotes in GnomAdExome4 at 7 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF6	NM_001001557.4	c.407-39C>G		intron_variant		ENST00000287020.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF6	ENST00000287020.7	c.407-39C>G		intron_variant		1	NM_001001557.4	P1

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 241 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000719

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00260

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00189 AC: 431 AN: 228560 Hom.: 1 AF XY: 0.00183 AC XY: 232 AN XY: 126840

Gnomad AFR exome AF: 0.000371

Gnomad AMR exome AF: 0.000176

Gnomad ASJ exome AF: 0.00133

Gnomad EAS exome AF: 0.0000572

Gnomad SAS exome AF: 0.00143

Gnomad FIN exome AF: 0.00146

Gnomad NFE exome AF: 0.00315

Gnomad OTH exome AF: 0.00189

GnomAD4 exome AF: 0.00245 AC: 3540 AN: 1444594 Hom.: 7 Cov.: 31 AF XY: 0.00246 AC XY: 1768 AN XY: 719002

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.000881

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00150

Gnomad4 FIN exome AF: 0.00199

Gnomad4 NFE exome AF: 0.00286

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.00162 AC XY: 121 AN XY: 74488

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000718

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.00260

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000928 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.74

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: rs77859767; hg19: chr8-97157791;