rs7135847

chr12-95183894-C-T

Variant summary

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

The NM_018351.4(FGD6):c.2442-11150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 151,972 control chromosomes in the GnomAD database, including 59,238 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 0.88 (59238 hom., cov: 32)
• Consequence: FGD6 NM_018351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

Genes affected

FGD6 (HGNC:21740): (FYVE, RhoGEF and PH domain containing 6) Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in several processes, including filopodium assembly; regulation of GTPase activity; and regulation of cell shape. Predicted to be located in Golgi apparatus; lamellipodium; and ruffle. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD6	NM_018351.4	c.2442-11150G>A		intron_variant		ENST00000343958.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD6	ENST00000343958.9	c.2442-11150G>A		intron_variant		1	NM_018351.4	P1
FGD6	ENST00000549499.1	c.2442-11150G>A		intron_variant		1
FGD6	ENST00000451107.3	c.17-11150G>A		intron_variant, NMD_transcript_variant		1
FGD6	ENST00000546711.5	c.2442-11150G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133642 AN: 151854 Hom.: 59177 Cov.: 32

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.824

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.892

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

GnomAD4 genome AF: 0.880 AC: 133763 AN: 151972 Hom.: 59238 Cov.: 32 AF XY: 0.884 AC XY: 65611 AN XY: 74262

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.893

Alfa AF: 0.858 Hom.: 9750

Bravo AF: 0.888

Asia WGS AF: 0.955 AC: 3320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	3.7
Dann	Benign	0.72

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: rs7135847; hg19: chr12-95577670;