rs9486880

Variant names:

• chr6-108418553-T-G
• rs9486880
• NM_145315.5:c.807+16499T>G

Variant summary

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

The NM_145315.5(AFG1L):​c.807+16499T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,002 control chromosomes in the GnomAD database, including 9,856 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 0.35 (9856 hom., cov: 31)
• Consequence: AFG1L NM_145315.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509

Genes affected

AFG1L (HGNC:16411): (AFG1 like ATPase) This gene encodes a mitochondrial integral membrane protein that plays a role in mitochondrial protein homeostasis. The protein contains a P-loop motif and a five-domain structure that is conserved in fly, yeast, and bacteria. It functions to mediate the degradation of nuclear-encoded complex IV subunits. Two conserved estrogen receptor binding sites are located within 2.5 kb of this gene. Polymorphisms in this gene have been associated with bipolar disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFG1L	NM_145315.5	c.807+16499T>G		intron_variant	Intron 7 of 12	ENST00000368977.9	NP_660358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFG1L	ENST00000368977.9	c.807+16499T>G		intron_variant	Intron 7 of 12	1	NM_145315.5	ENSP00000357973.3
AFG1L	ENST00000421954.5	c.408+16499T>G		intron_variant	Intron 5 of 10	5		ENSP00000398225.1
AFG1L	ENST00000431865.1	n.230-28661T>G		intron_variant	Intron 2 of 7	5		ENSP00000415484.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53514 AN: 151884 Hom.: 9858 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.352 AC: 53522 AN: 152002 Hom.: 9856 Cov.: 31 AF XY: 0.347 AC XY: 25768 AN XY: 74264

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.383

Alfa AF: 0.412 Hom.: 19195

Bravo AF: 0.346

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.53

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: rs9486880; hg19: chr6-108739757;